Current and emerging avenues for Alzheimer's disease drug targets.
AD gene therapy
AD molecular targets
AD therapeutics
Tau therapies
alzheimer´s disease
amyloid beta therapies
Journal
Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
pubmed:
10
7
2019
medline:
26
5
2020
entrez:
10
7
2019
Statut:
ppublish
Résumé
Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Aβ) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Aβ and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood-brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near-future strategy.
Substances chimiques
Amyloid beta-Peptides
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
398-437Informations de copyright
© 2019 The Association for the Publication of the Journal of Internal Medicine.
Références
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 2007; 3: 186-91.
Brookmeyer R, Evans DA, Hebert L et al. National estimates of the prevalence of Alzheimer's disease in the United States. Alzheimers Dement 2011; 7: 61-73.
Ferri CP, Prince M, Brayne C et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112-7.
Winblad B, Amouyel P, Andrieu S et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol 2016; 15: 455-532.
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006; 367: 1747-57.
Farrer LA, Cupples LA, Haines JL et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA 1997; 278: 1349-56.
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013; 9: 63-75 e2.
Wimo A, Guerchet M, Ali GC et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 2017; 13: 1-7.
Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 2016; 8: 23.
Wimo A, Jonsson L, Bond J, Prince M, Winblad B, Alzheimer Disease I. The worldwide economic impact of dementia 2010. Alzheimers Dement 2013; 9: 1-11 e3.
Clark BF. Healthy human ageing. N Biotechnol 2008; 25: 13-5.
Daskalopoulou C, Stubbs B, Kralj C, Koukounari A, Prince M, Prina AM. Associations of smoking and alcohol consumption with healthy ageing: a systematic review and meta-analysis of longitudinal studies. BMJ Open 2018; 8: e019540.
Schneider LS, Mangialasche F, Andreasen N et al. Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med 2014; 275: 251-83.
Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer's disease: clinical trials and drug development. Lancet Neurol 2010; 9: 702-16.
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256: 184-5.
Karran E, De Strooper B. The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem 2016; 139(Suppl. 2): 237-52.
Hardy J, De Strooper B. Alzheimer's disease: where next for anti-amyloid therapies? Brain 2017; 140: 853-5.
Pugazhenthi S. Metabolic syndrome and the cellular phase of Alzheimer's disease. Prog Mol Biol Transl Sci 2017; 146: 243-58.
De Strooper B, Karran E. The cellular phase of Alzheimer's disease. Cell 2016; 164: 603-15.
McGeer PL, McGeer EG. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol 2013; 126: 479-97.
Sarazin M, Dorothee G, de Souza LC, Aucouturier P. Immunotherapy in Alzheimer's disease: do we have all the pieces of the puzzle? Biol Psychiatry 2013; 74: 329-32.
Loera-Valencia R, Piras A, Ismail MAM et al. Targeting Alzheimer's disease with gene and cell therapies. J Intern Med 2018; 284: 2-36.
Kemppainen N, Johansson J, Teuho J et al. Brain amyloid load and its associations with cognition and vascular risk factors in FINGER study. Neurology 2018; 90: e206-13.
Worker A, Dima D, Combes A et al. Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations. Hum Brain Mapp 2018; 39: 1743-54.
Fraser MA, Shaw ME, Cherbuin N. A systematic review and meta-analysis of longitudinal hippocampal atrophy in healthy human ageing. NeuroImage 2015; 112: 364-74.
Vos SJB, Gordon BA, Su Y et al. NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers. Neurobiol Aging 2016; 44: 1-8.
Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 1996; 92: 197-201.
Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 2006; 27: 1372-84.
Klein WL. Synaptic targeting by Aβ oligomers (ADDLS) as a basis for memory loss in early Alzheimer's disease. Alzheimers Dement 2006; 2: 43-55.
Lacor PN, Buniel MC, Furlow PW et al. A oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 2007; 27: 796-807.
Wang H-W, Pasternak JF, Kuo H et al. Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res 2002; 924: 133-40.
Esteves da Silva M, Adrian M, Schätzle P et al. Positioning of AMPA receptor-containing endosomes regulates synapse architecture. Cell Rep 2015; 13: 933-43.
Angelo M, Plattner F, Giese KP. Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory. J Neurochem 2006; 99: 353-70.
Leshchyns'ka I, Sytnyk V. Synaptic cell adhesion molecules in Alzheimer's disease. Neural Plast 2016; 2016: 1-9.
Eyjolfsdottir H, Eriksdotter M, Linderoth B et al. Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device. Alzheimers Res Ther 2016; 8: 30.
Bothwell M. NFG, BDNF, NT3, and NT4. In: Lewin GR, Carter BD, eds. Neurotrophic Factors. Berlin and Heidelberg: Springer, 2014; 3-15.
Miyamoto A, Wake H, Ishikawa AW et al. Microglia contact induces synapse formation in developing somatosensory cortex. Nat Commun 2016; 7: 12540.
Haraguchi S, Sasahara K, Shikimi H, Honda S-i, Harada N, Tsutsui K. Estradiol promotes purkinje dendritic growth, spinogenesis, and synaptogenesis during neonatal life by inducing the expression of BDNF. Cerebellum 2011; 11: 416-7.
Dave KA, Platel J-C, Huang F, Tian D, Stamboulian-Platel S, Bordey A. Prostaglandin E2 induces glutamate release from subventricular zone astrocytes. Neuron Glia Biol 2010; 6: 201-7.
Batti L, O'Connor JJ. Tumor necrosis factor-α impairs the recovery of synaptic transmission from hypoxia in rat hippocampal slices. J Neuroimmunol 2010; 218: 21-7.
Dupont C, Armant D, Brenner C. Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med 2009; 27: 351-7.
Rogers J, Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD. The epigenetics of Alzheimer's disease - additional considerations. Neurobiol Aging 2011; 32: 1196-7.
Neal M, Richardson JR. Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration. Biochim Biophys Acta 1864, 2018,; 432-43.
Feligioni M, Nisticò R. SUMO: a (oxidative) stressed protein. NeuroMol Med 2013; 15: 707-19.
Li T, Santockyte R, Shen R-F et al. Expression of SUMO-2/3 induced senescence through p53- and pRB-mediated pathways. J Biol Chem 2006; 281: 36221-7.
Fiore R, Khudayberdiev S, Saba R. Schratt G. microRNA function in the nervous system. Prog Mol Biol Transl Sci 2011; 47-100.
Putteeraj M, Fairuz YM, Teoh SL. MicroRNA dysregulation in Alzheimer's disease. CNS Neurol Disord Drug Targets 2018; 16.
Goedeke L, Fernández-Hernando C. microRNAs: a connection between cholesterol metabolism and neurodegeneration. Neurobiol Dis 2014; 72: 48-53.
Heneka MT, Carson MJ, Khoury JE et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015; 14: 388-405.
Obermeier B, Verma A, Ransohoff RM. The blood-brain barrier. Handbook Clin Neurol 2016; 39-59.
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harbor Perspec Bio 2015; 7: a020412.
Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci 2016; 19: 771-83.
Cheslow L, Alvarez JI. Glial-endothelial crosstalk regulates blood-brain barrier function. Curr Opin Pharmacol 2016; 26: 39-46.
Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163: 1064-78.
Mahringer A, Fricker G. ABC transporters at the blood-brain barrier. Expert Opin Drug Metab Toxicol 2016; 12: 499-508.
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 2011; 12: 723-38.
Vanlandewijck M, He L, Mae MA et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 2018; 554: 475-80.
Erdő F, Denes L, de Lange E. Age-associated physiological and pathological changes at the blood-brain barrier: a review. J Cereb Blood Flow Metab 2016; 37: 4-24.
van de Haar HJ, Burgmans S, Jansen JFA et al. Blood-brain barrier leakage in patients with early Alzheimer disease. Radiology 2016; 281: 527-35.
Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 2018; 14: 133-50.
Poliakova T, Levin O, Arablinskiy A, Vasenina E, Zerr I. Cerebral microbleeds in early Alzheimer's disease. J Neurol 2016; 263: 1961-8.
Deo AK, Borson S, Link JM et al. Activity of P-glycoprotein, a -amyloid transporter at the blood-brain barrier, is compromised in patients with mild Alzheimer disease. J Nucl Med 2014; 55: 1106-11.
Bailey TL, Rivara CB, Rocher AB, Hof PR. The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease. Neurol Res 2004; 26: 573-8.
Lepelletier FX, Mann DMA, Robinson AC, Pinteaux E, Boutin H. Early changes in extracellular matrix in Alzheimer's disease. Neuropathol Appl Neurobiol 2015; 43: 167-82.
Halliday MR, Rege SV, Ma Q et al. Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease. J Cereb Blood Flow Metab 2015; 36: 216-27.
Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta 2016; 1862: 887-900.
Bagyinszky E, Giau VV, Shim K, Suk K, An SSA, Kim S. Role of inflammatory molecules in the Alzheimer's disease progression and diagnosis. J Neurol Sci 2017; 376: 242-54.
Laurent C, Dorothée G, Hunot S et al. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy. Brain 2016; 140: 184-200.
Krauthausen M, Kummer MP, Zimmermann J et al. CXCR69 promotes plaque formation and behavioral deficits in an Alzheimer's disease model. J Clin Invest 2014; 125: 365-78.
Torres KCL, Santos RR, de Lima GSF et al. Decreased expression of CCL3 in monocytes and CCR70 in lymphocytes from frontotemporal dementia as compared with Alzheimer's disease patients. J Neuropsy Clin Neurosci 2012; 24: E11-2.
Zhu M, Allard JS, Zhang Y et al. Age-related brain expression and regulation of the chemokine CCL4/MIP-1β in APP/PS1 double-transgenic mice. J Neuropathol Exp Neurol 2014; 73: 362-74.
Franciosi S, Choi HB, Kim SU, McLarnon JG. IL-8 enhancement of amyloid-beta (Aβ1-42)-induced expression and production of pro-inflammatory cytokines and COX-2 in cultured human microglia. J Neuroimmunol 2005; 159: 66-74.
Fuhrmann M, Bittner T, Jung CKE et al. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci 2010; 13: 411-3.
Tripathy D, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer's disease brain: a possible neuroprotective role. Neurobiol Aging 2010; 31: 8-16.
Lee JK, Schuchman EH, Jin HK, Bae J-S. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid β ameliorates Alzheimer's disease in mice by recruiting bone marrow-induced microglia immune responses. Stem Cells 2012; 30: 1544-55.
Naert G, Rivest S. CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. J Neurosci 2011; 31: 6208-20.
Kiyota T, Yamamoto M, Xiong H et al. CCL2 accelerates microglia-mediated Aβ oligomer formation and progression of neurocognitive dysfunction. PLoS ONE 2009; 4: e6197.
Yamamoto M, Horiba M, Buescher JL et al. Overexpression of monocyte chemotactic protein-1/CCL2 in β-amyloid precursor protein transgenic mice show accelerated diffuse β-amyloid deposition. Am J Pathol 2005; 166: 1475-85.
Verite J, Janet T, Julian A, Chassaing D, Page G, Paccalin M. Peripheral blood mononuclear cells of Alzheimer's disease patients control CCL4 and CXCL10 levels in a human blood brain barrier model. Curr Alzheimer Res 2017; 14.
Verite J, Janet T, Chassaing D, Fauconneau B, Rabeony H, Page G. Longitudinal chemokine profile expression in a blood-brain barrier model from Alzheimer transgenic versus wild-type mice. J Neuroinflamm 2018; 15: 182.
Gorelick PB, Scuteri A, Black SE et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 2672-713.
Maillard P, Seshadri S, Beiser A et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 2012; 11: 1039-47.
Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12: 483-97.
Yoshino H, Sakurai T, Oizumi XS et al. Dilation of perforating arteries in rat brain in response to systemic hypotension is more sensitive and pronounced than that of pial arterioles: simultaneous visualization of perforating and cortical vessels by in-vivo microangiography. Microvasc Res 2009; 77: 230-3.
Hainsworth AH, Markus HS. Do in vivo experimental models reflect human cerebral small vessel disease? a systematic review. J Cereb Blood Flow Metab 2008; 28: 1877-91.
Schreiber S, Bueche CZ, Garz C et al. Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats. PLoS ONE 2011; 6: e26287.
Schreiber S, Bueche CZ, Garz C et al. The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cereb Blood Flow Metab 2012; 32: 278-90.
Bailey EL, Wardlaw JM, Graham D, Dominiczak AF, Sudlow CLM, Smith C. Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol 2011; 37: 711-26.
Kaiser D, Weise G, Möller K et al. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun 2014; 2.
Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 1988; 31: 47-59.
den Heijer T, Launer LJ, Prins ND et al. Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology 2005; 64: 263-7.
Sabbatini M, Catalani A, Consoli C, Marletta N, Tomassoni D, Avola R. The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia? Mech Ageing Dev 2002; 123: 547-59.
Leeuw FE, Kleine M, Frijns CJM, Fijnheer R, Gijn J, Kappelle LJ. Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease. Ann N Y Acad Sci 2002; 977: 306-14.
Schiffrin EL. Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond) 2014; 126: 267-74.
Moller K, Posel C, Kranz A et al. Arterial hypertension aggravates innate immune responses after experimental stroke. Front Cell Neurosci 2015; 9: 461.
Tummala PE, Chen XL, Sundell CL et al. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: a potential link between the renin-angiotensin system and atherosclerosis. Circulation 1999; 100: 1223-9.
Rouhl RP, Damoiseaux JG, Lodder J et al. Vascular inflammation in cerebral small vessel disease. Neurobiol Aging 2012; 33: 1800-6.
Harrison DG, Marvar PJ, Titze JM. Vascular inflammatory cells in hypertension. Front Physiol 2012; 3.
Derecki NC, Cardani AN, Yang CH et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 2010; 207: 1067-80.
van Weel V, Toes RE, Seghers L et al. Natural killer cells and CD4+ T-cells modulate collateral artery development. Arterioscler Thromb Vasc Biol 2007; 27: 2310-8.
Rosenberg A, Ngandu T, Rusanen M et al. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: the FINGER trial. Alzheimers Dement 2018; 14: 263-70.
Martinez-Ramirez S, Greenberg SM, Viswanathan A. Cerebral microbleeds: overview and implications in cognitive impairment. Alzheimers Res Ther 2014; 6: 33.
Ding J, Sigurðsson S, Jónsson PV et al. Space and location of cerebral microbleeds, cognitive decline, and dementia in the community. Neurology 2017; 88: 2089-97.
Matsuyama H, Ii Y, Maeda M et al. Background and distribution of lobar microbleeds in cognitive dysfunction. Brain Behav 2017; 7: e00856.
Hilal S, Akoudad S, van Duijn CM et al. Plasma amyloid-β levels, cerebral small vessel disease, and cognition: the Rotterdam study. J Alzheimers Dis 2017; 60: 977-87.
Stehling C, Wersching H, Kloska SP et al. Detection of asymptomatic cerebral microbleeds: a comparative study at 1.5 and 3.0 T. Acad Radiol 2008; 15: 895-900.
Vernooij MW, van der Lugt A, Ikram MA et al. Prevalence and risk factors of cerebral microbleeds: the Rotterdam scan study. Neurology 2008; 70: 1208-14.
Kumar P, Yadav AK, Misra S, Kumar A, Chakravarty K, Prasad K. Prediction of upper extremity motor recovery after subacute intracerebral hemorrhage through diffusion tensor imaging: a systematic review and meta-analysis. Neuroradiology 2016; 58: 1043-50.
Karuppagounder SS, Alim I, Khim SJ et al. Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med 2016; 8: 328ra29-ra29.
Zille M, Karuppagounder SS, Chen Y et al. Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis. Stroke 2017; 48: 1033-43.
Raff MC, Whitmore AV, Finn JT. Axonal self-destruction and neurodegeneration. Science 2002; 296: 868-71.
Sagot Y, Dubois-Dauphin M, Tan SA et al. Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease. J Neurosci 1995; 15: 7727-33.
Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 2009; 457: 981-9.
Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 2015; 16: 358-72.
Zotova E, Nicoll JA, Kalaria R, Holmes C, Boche D. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimers Res Ther 2010; 2: 1.
Sommer F, Backhed F. The gut microbiota-masters of host development and physiology. Nat Rev Microbiol 2013; 11: 227-38.
Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489: 242-9.
Claesson MJ, Jeffery IB, Conde S et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488: 178-84.
Marizzoni M, Provasi S, Cattaneo A, Frisoni GB. Microbiota and neurodegenerative diseases. Curr Opin Neurol 2017; 30: 630-8.
Cattaneo A, Cattane N, Galluzzi S et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 2017; 49: 60-8.
Russler-Germain EV, Rengarajan S, Hsieh CS. Antigen-specific regulatory T-cell responses to intestinal microbiota. Mucosal Immunol 2017; 10: 1375-86.
Braniste V, Al-Asmakh M, Kowal C et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 2014; 6: 263ra158.
Dantzer R. Neuroimmune interactions: from the brain to the immune system and vice versa. Physiol Rev 2018; 98: 477-504.
Soscia SJ, Kirby JE, Washicosky KJ et al. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS ONE 2010; 5: e9505.
Kumar DK, Choi SH, Washicosky KJ et al. Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci Transl Med 2016; 8: 340ra72.
Pulze L, Bassani B, Gini E et al. NET amyloidogenic backbone in human activated neutrophils. Clin Exp Immunol 2016; 183: 469-79.
Pisa D, Alonso R, Rabano A, Rodal I, Carrasco L. Different brain regions are infected with fungi in Alzheimer's disease. Sci Rep 2015; 5: 15015.
Zhao Y, Cong L, Lukiw WJ. Lipopolysaccharide (LPS) accumulates in neocortical neurons of Alzheimer's disease (AD) brain and impairs transcription in human neuronal-glial primary co-cultures. Front Aging Neurosci 2017; 9: 407.
Franzosa EA, Huang K, Meadow JF et al. Identifying personal microbiomes using metagenomic codes. Proc Natl Acad Sci USA 2015; 112: E2930-8.
Akbari E, Asemi Z, Daneshvar Kakhaki R et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front Aging Neurosci 2016; 8: 256.
Jarosz-Griffiths HH, Noble E, Rushworth JV, Hooper NM. Amyloid-β receptors: the good, the bad, and the prion protein. J Biol Chem 2015; 291: 3174-83.
Miklossy J, Qing H, Radenovic A et al. Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes. Neurobiol Aging 2010; 31: 1503-15.
Roher AE, Cribbs DH, Kim RC et al. Bapineuzumab alters Abeta composition: implications for the amyloid cascade hypothesis and anti-amyloid immunotherapy. PLoS ONE 2013; 8: e59735.
Yang Y, Wu Y, Zhang S, Song W. High glucose promotes Aβ production by inhibiting APP degradation. PLoS ONE 2013; 8: e69824.
Takeda S, Sato N, Uchio-Yamada K et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci USA 2010; 107: 7036-41.
Bharadwaj P, Solomon T, Malajczuk CJ et al. Role of the cell membrane interface in modulating production and uptake of Alzheimer's beta amyloid protein. Biochem Biophys Acta 2018.
Balczon R. The identification, purification, and characterization of a pancreatic beta-cell form of the microtubule adenosine triphosphatase kinesin. Endocrinology 1992; 131: 331-6.
Alvim RO, Cheuhen MR, Machado SR, Sousa AGP, Santos PCJL. General aspects of muscle glucose uptake. An Acad Bras Ciênc 2015; 87: 351-68.
Emoto M, Langille SE, Czech MP. A role for kinesin in insulin-stimulated GLUT4 glucose transporter translocation in 3T3-L1 adipocytes. J Biol Chem 2001; 276: 10677-82.
Olson AL, Trumbly AR, Gibson GV. Insulin-mediated GLUT4 translocation is dependent on the microtubule network. J Biol Chem 2001; 276: 10706-14.
Porte D, Baskin DG, Schwartz MW. Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes 2005; 54: 1264-76.
Yin F, Yao J, Sancheti H et al. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity. Neurobiol Aging 2015; 36: 2282-95.
Moreira PI, Santos MS, Sena C, Seica R, Oliveira CR. Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats. Neurobiol Dis 2005; 18: 628-37.
Duarte AI, Proenca T, Oliveira CR, Santos MS, Rego AC. Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress. Diabetes 2006; 55: 2863-70.
Santos RX, Correia SC, Alves MG et al. Insulin therapy modulates mitochondrial dynamics and biogenesis, autophagy and tau protein phosphorylation in the brain of type 1 diabetic rats. Biochim Biophys Acta 2014; 1842: 1154-66.
Duarte AI, Santos MS, Oliveira CR, Rego AC. Insulin neuroprotection against oxidative stress in cortical neurons-involvement of uric acid and glutathione antioxidant defenses. Free Radic Biol Med 2005; 39: 876-89.
Duarte AI, Santos P, Oliveira CR, Santos MS, Rego AC. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. Biochim Biophys Acta 2008; 1783: 994-1002.
Duarte AI, Santos MS, Seica R, Oliveira CR. Oxidative stress affects synaptosomal-aminobutyric acid and glutamate transport in diabetic rats: the role of insulin. Diabetes 2004; 53: 2110-6.
Duarte AI, Santos MS. Seiça R, oliveira CRd. Insulin affects synaptosomal GABA and glutamate transport under oxidative stress conditions. Brain Res 2003; 977: 23-30.
De Felice FG, Benedict C. A key role of insulin receptors in memory: figure 1. Diabetes 2015; 64: 3653-5.
Rodriguez-Rodriguez P, Sandebring-Matton A, Merino-Serrais P et al. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons. Brain 2017; 140: 3269-85.
Kullmann S, Heni M, Hallschmid M, Fritsche A, Preissl H, Häring H-U. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol Rev 2016; 96: 1169-209.
Zhao L, Mao Z, Woody SK, Brinton RD. Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease. Neurobiol Aging 2016; 42: 69-79.
Brinton RD, Yao J, Yin F, Mack WJ, Cadenas E. Perimenopause as a neurological transition state. Nat Rev Endocrinol 2015; 11: 393-405.
Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta 1842, 2014,; 1219-31.
Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta 1863, 2017,; 1078-89.
Winblad B, Qiu C, Ballard C, Johansson G. Evidence-based prevention and treatment of dementia - Authors’ reply. Lancet Neurol 2016; 15: 1007-8.
Pearson-Leary J, Jahagirdar V, Sage J, McNay EC. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4. Behav Brain Res 2018; 338: 32-9.
Winkler EA, Nishida Y, Sagare AP et al. GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration. Nat Neurosci 2015; 18: 521-30.
Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol 2011; 10: 187-98.
Cunnane S, Nugent S, Roy M et al. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition 2011; 27: 3-20.
Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease. Hum Mol Genet 2011; 20: 4515-29.
Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE. Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 2005; 57: 695-703.
Melo JB, Agostinho P, Oliveira CR. Amyloid beta-peptide 25-35 reduces [3H]acetylcholine release in retinal neurons. Involvement of metabolic dysfunction. Amyloid 2002; 9: 221-8.
Onyango IG, Dennis J, Khan SM. Mitochondrial dysfunction in Alzheimer's disease and the rationale for bioenergetics based therapies. Aging Dis 2016; 7: 201-14.
Yao J, Zhao L, Mao Z et al. Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor beta-selective phytoSERM treatments. Brain Res 2013; 1514: 128-41.
Fang D, Wang Y, Zhang Z et al. Increased neuronal PreP activity reduces Abeta accumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model. Hum Mol Genet 2015; 24: 5198-210.
Yao J, Irwin R, Chen S, Hamilton R, Cadenas E, Brinton RD. Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid. Neurobiol Aging 2012; 33: 1507-21.
Mosconi L, de Leon M, Murray J et al. Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease. J Alzheimers Dis 2011; 27: 483-90.
Swerdlow RH. Mitochondria and cell bioenergetics: increasingly recognized components and a possible etiologic cause of Alzheimer's disease. Antioxid Redox Signal 2012; 16: 1434-55.
Yu Q, Du F, Douglas JT, Yu H, Yan SS, Yan SF. Mitochondrial dysfunction triggers synaptic deficits via activation of p38 MAP kinase signaling in differentiated Alzheimer's disease trans-mitochondrial cybrid cells. J Alzheimers Dis 2017; 59: 223-39.
Amorim JA, Canas PM, Tome AR et al. Mitochondria in excitatory and inhibitory synapses have similar susceptibility to amyloid-beta peptides modeling Alzheimer's disease. J Alzheimers Dis 2017; 60: 525-36.
Fang D, Yan S, Yu Q, Chen D, Yan SS. Mfn2 is required for mitochondrial development and synapse formation in human induced pluripotent stem cells/hiPSC derived cortical neurons. Sci Rep 2016; 6: 31462.
Gan X, Huang S, Wu L et al. Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer's disease cybrid cell. Biochim Biophys Acta 2014; 1842: 220-31.
Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci USA 2010; 107: 18670-5.
Tortelli R, Lozupone M, Guerra V et al. Midlife metabolic profile and the risk of late-life cognitive decline. J Alzheimers Dis 2017; 59: 121-30.
Mosconi L, Murray J, Tsui WH et al. Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD. Neurology 2014; 82: 752-60.
Verdile G, Fuller SJ, Martins RN. The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 2015; 84: 22-38.
Verdile G, Laws SM, Henley D et al. Associations between gonadotropins, testosterone and beta amyloid in men at risk of Alzheimer's disease. Mol Psychiatry 2014; 19: 69-75.
Duarte AI, Santos MS, Oliveira CR, Moreira PI. Brain insulin signalling, glucose metabolism and females’ reproductive aging: a dangerous triad in Alzheimer's disease. Neuropharmacology 2018; 136: 223-42.
Medina M, Avila J. New perspectives on the role of tau in Alzheimer's disease. Implications for therapy. Biochem Pharmacol 2014; 88: 540-7.
Shaikh S, Rizvi SM, Shakil S, Riyaz S, Biswas D, Jahan R. Forxiga (dapagliflozin): plausible role in the treatment of diabetes-associated neurological disorders. Biotechnol Appl Biochem 2016; 63: 145-50.
Corbett A, Ballard C. Is a potential Alzheimer's therapy already in use for other conditions? Can medications for hypertension, diabetes and acne help with the symptoms? Expert Opin Investig Drugs 2013; 22: 941-3.
Sandhir R, Gupta S. Molecular and biochemical trajectories from diabetes to Alzheimer's disease: a critical appraisal. World J Diabetes 2015; 6: 1223-42.
Sebastiao I, Candeias E, Santos MS, de Oliveira CR, Moreira PI, Duarte AI. Insulin as a bridge between type 2 diabetes and alzheimer disease - how anti-diabetics could be a solution for dementia. Front Endocrinol (Lausanne) 2014; 5: 110.
Ahmed S, Mahmood Z, Javed A et al. Effect of metformin on adult hippocampal neurogenesis: comparison with donepezil and links to cognition. J Mol Neurosci 2017; 62: 88-98.
Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav 2012; 101: 564-74.
Carvalho C, Correia S, Santos MS, Seiça R, Oliveira CR, Moreira PI. Metformin promotes isolated rat liver mitochondria impairment. Mol Cell Biochem 2007; 308: 75-83.
Hsu CC, Wahlqvist ML, Lee MS, Tsai HN. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. J Alzheimers Dis 2011; 24: 485-93.
Cai Z, Ratka A. Opioid system and Alzheimer's disease. NeuroMol Med 2012; 14: 91-111.
Moore EM, Mander AG, Ames D et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 2013; 36: 2981-7.
Tahrani AA, Barnett AH, Bailey CJ. Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus. Nat Rev Endocrinol 2016; 12: 566-92.
Imfeld P, Bodmer M, Jick SS, Meier CR. Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J Am Geriatr Soc 2012; 60: 916-21.
Gavin JR 3rd, Stolar MW, Freeman JS, Spellman CW. Improving outcomes in patients with type 2 diabetes mellitus: practical solutions for clinical challenges. J Am Osteopath Assoc 2010; 110: S2-14; quiz S5-6.
Tureyen K, Kapadia R, Bowen KK et al. Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. J Neurochem 2007; 101: 41-56.
Peymani M, Ghoochani A, Ghaedi K et al. Dual effects of peroxisome proliferator-activated receptor γ on embryonic stem cell self-renewal in presence and absence of leukemia inhibitory factor. Eur J Cell Biol 2013; 92: 160-8.
Risner ME, Saunders AM, Altman JFB et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 2006; 6: 246-54.
Gold M, Alderton C, Zvartau-Hind M et al. Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord 2010; 30: 131-46.
Morsink LM, Smits MM, Diamant M. Advances in pharmacologic therapies for type 2 diabetes. Curr Atheroscler Rep 2013; 15.
Craft S. Insulin and Alzheimer disease-reply. Arch Neurol 2012; 69: 670.
Naia L, Ferreira IL, Cunha-Oliveira T et al. Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's disease human lymphoblasts. Mol Neurobiol 2014; 51: 331-48.
Naia L, Ribeiro M, Rodrigues J et al. Insulin and IGF-1 regularize energy metabolites in neural cells expressing full-length mutant huntingtin. Neuropeptides 2016; 58: 73-81.
Lopes C, Ribeiro M, Duarte AI et al. IGF-1 intranasal administration rescues Huntington's disease phenotypes in YAC128 mice. Mol Neurobiol 2013; 49: 1126-42.
Duarte AI, Petit GH, Ranganathan S et al. IGF-1 protects against diabetic features in an in vivo model of Huntington's disease. Exp Neurol 2011; 231: 314-9.
Pandini G, Pace V, Copani A, Squatrito S, Milardi D, Vigneri R. Insulin has multiple antiamyloidogenic effects on human neuronal cells. Endocrinology 2013; 154: 375-87.
De Felice FG, Lourenco MV, Ferreira ST. How does brain insulin resistance develop in Alzheimer's disease? Alzheimers Dement 2014; 10: S26-32.
De Felice FG, Vieira MN, Bomfim TR et al. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci USA 2009; 106: 1971-6.
Cardoso S, Santos RX, Correia SC et al. Insulin-induced recurrent hypoglycemia exacerbates diabetic brain mitochondrial dysfunction and oxidative imbalance. Neurobiol Dis 2013; 49: 1-12.
Cardoso S, Carvalho C, Santos R et al. Impact of STZ-induced hyperglycemia and insulin-induced hypoglycemia in plasma amino acids and cortical synaptosomal neurotransmitters. Synapse 2010; 65: 457-66.
Maimaiti S, Frazier HN, Anderson KL et al. Novel calcium-related targets of insulin in hippocampal neurons. Neuroscience 2017; 364: 130-42.
Craft S, Claxton A, Baker LD et al. Effects of regular and long-acting insulin on cognition and Alzheimer's disease biomarkers: a pilot clinical trial. J Alzheimers Dis 2017; 57: 1325-34.
Reger MA, Watson GS, Green PS et al. Intranasal insulin improves cognition and modulates -amyloid in early AD. Neurology 2007; 70: 440-8.
Ghasemi R, Dargahi L, Haeri A, Moosavi M, Mohamed Z, Ahmadiani A. Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders. Mol Neurobiol 2013; 47: 1045-65.
Candeias EM. Gut-brain connection: the neuroprotective effects of the anti-diabetic drug liraglutide. World J Diabetes 2015; 6: 807.
Stolar MW, Grimm M, Chen S. Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2013; 6: 435-44.
Montanya E. A comparison of currently available GLP-1 receptor agonists for the treatment of type 2 diabetes. Expert Opin Pharmacother 2012; 13: 1451-67.
Hamilton A, Patterson S, Porter D, Gault VA, Holscher C. Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J Neurosci Res 2011; 89: 481-9.
D'Amico M, Di Filippo C, Marfella R et al. Corrigendum to “LONG-TERM inhibition of dipeptidyl peptidase-4 in Alzheimer's prone mice” [Exp. Gerontol. (2010) 202-207]. Exp Gerontol 2013; 48: 1002.
Beeri MS, Schmeidler J, Silverman JM et al. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology 2008; 71: 750-7.
Pintana H, Apaijai N, Chattipakorn N, Chattipakorn SC. DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats. J Endocrinol 2013; 218: 1-11.
Darsalia V, Klein T, Nystrom T, Patrone C. Glucagon-like receptor 1 agonists and DPP-4 inhibitors: anti-diabetic drugs with anti-stroke potential. Neuropharmacology 2018; 136: 280-6.
Kosaraju J, Murthy V, Khatwal RB et al. Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease. J Pharm Pharmacol 2013; 65: 1773-84.
Bae C, Song J. The role of glucagon-like peptide 1 (GLP1) in type 3 diabetes: GLP-1 controls insulin resistance, neuroinflammation and neurogenesis in the brain. Int J Mol Sci 2017; 18: 2493.
Li Z, Ni C-L, Yao Z, Chen L-M, Niu W-Y. Liraglutide enhances glucose transporter 4 translocation via regulation of AMP-activated protein kinase signaling pathways in mouse skeletal muscle cells. Metabolism 2014; 63: 1022-30.
Li Y, Li L, Holscher C. Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases. Rev Neurosci 2016; 27: 689-711.
Muscogiuri G, DeFronzo RA, Gastaldelli A, Holst JJ. Glucagon-like peptide-1 and the central/peripheral nervous system: crosstalk in diabetes. Trends Endocrinol Metab 2017; 28: 88-103.
Kickstein E, Krauss S, Thornhill P et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci USA 2010; 107: 21830-5.
Majewski C, Bakris GL. Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: table 1. Diabetes Care 2015; 38: 429-30.
Solini A. Extra-glycaemic properties of empagliflozin. Diabetes Metab Res Rev 2015; 32: 230-7.
Cai HY, Wang ZJ, Holscher C et al. Lixisenatide attenuates the detrimental effects of amyloid beta protein on spatial working memory and hippocampal neurons in rats. Behav Brain Res 2017; 318: 28-35.
Ferrannini E, Muscelli E, Frascerra S et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 2014; 124: 499-508.
Solini A. Extra-glycaemic properties of empagliflozin. Diabetes Metab Res Rev 2016; 32: 230-7.
Vickers SP, Cheetham SC, Headland KR et al. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet. Diabetes Metab Syndr Obes 2014; 7: 265-75.
Chilton R, Tikkanen I, Crowe S, Johansen OE, Broedl UC, Woerle HJ, Hach T. Empagliflozin reduces systolic blood pressure in dipper and non-dipper patients with type 2 diabetes and hypertension. Am Heart Assoc 2014.
Tikkanen I, Chilton R, Johansen OE. Potential role of sodium glucose cotransporter 2 inhibitors in the treatment of hypertension. Curr Opin Nephrol Hypertens 2016; 25: 81-6.
Ott C, Jumar A, Striepe K et al. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol 2017; 16: 26.
Lin B, Koibuchi N, Hasegawa Y et al. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol 2014; 13: 148.
Millar P, Pathak N, Parthsarathy V et al. Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. J Endocrinol 2017; 234: 255-67.
Di Paolo G, Kim TW. Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci 2011; 12: 284-96.
Karasinska JM, Hayden MR. Cholesterol metabolism in Huntington disease. Nat Rev Neurol 2011; 7: 561-72.
Jones L, Holmans PA, Hamshere ML et al. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease. PLoS ONE 2010; 5: e13950.
Zissimopoulos JM, Barthold D, Brinton RD, Joyce G. Sex and race differences in the association between statin use and the incidence of Alzheimer disease. JAMA Neurol 2017; 74: 225-32.
Petek B, Villa-Lopez M, Loera-Valencia R et al. Connecting the brain cholesterol and renin-angiotensin systems: potential role of statins and RAS-modifying medications in dementia. J Intern Med 2018; 284: 620-42.
Bjorkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 2004; 24: 806-15.
Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA 1999; 96: 7238-43.
Bjorkhem I, Diczfalusy U. 24(S),25-epoxycholesterol-a potential friend. Arterioscler Thromb Vasc Biol 2004; 24: 2209-10.
Sodero AO, Trovo L, Iannilli F, Van Veldhoven P, Dotti CG, Martin MG. Regulation of tyrosine kinase B activity by the Cyp46/cholesterol loss pathway in mature hippocampal neurons: relevance for neuronal survival under stress and in aging. J Neurochem 2011; 116: 747-55.
Lutjohann D, Breuer O. vol 931996; 9799-804.
Burlot MA, Braudeau J, Michaelsen-Preusse K et al. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology. Hum Mol Genet 2015; 24: 5965-76.
Djelti F, Braudeau J, Hudry E et al. CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease. Brain 2015; 138: 2383-98.
Hudry E, Van Dam D, Kulik W et al. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease. Mol Ther 2010; 18: 44-53.
Lannfelt L, Moller C, Basun H et al. Perspectives on future Alzheimer therapies: amyloid-beta protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease. Alzheimers Res Ther 2014; 6: 16.
Boussicault L, Alves S, Lamaziere A et al. CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington's disease. Brain 2016; 139: 953-70.
Piguet F, Alves S, Cartier N. Clinical gene therapy for neurodegenerative diseases: past, present, and future. Hum Gene Ther 2017; 28: 988-1003.
Orth M, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol 2012; 2012: 292598.
Cedazo-Minguez A, Ismail MA, Mateos L. Plasma cholesterol and risk for late-onset Alzheimer's disease. Expert Rev Neurother 2011; 11: 495-8.
Kivipelto M, Ngandu T, Fratiglioni L et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005; 62: 1556-60.
Kivipelto M, Helkala EL, Laakso MP et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002; 137: 149-55.
Cedazo-Minguez A, Cowburn RF. Apolipoprotein E: a major piece in the Alzheimer's disease puzzle. J Cell Mol Med 2001; 5: 254-66.
Bjorkhem I, Cedazo-Minguez A, Leoni V, Meaney S. Oxysterols and neurodegenerative diseases. Mol Aspects Med 2009; 30: 171-9.
Bjorkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med 2006; 260: 493-508.
Lutjohann D, Bjorkhem I, Locatelli S et al. Cholesterol dynamics in the foetal and neonatal brain as reflected by circulatory levels of 24S-hydroxycholesterol. Acta Paediatr 2001; 90: 652-7.
Meaney S, Hassan M, Sakinis A et al. Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study. J Lipid Res 2001; 42: 70-8.
Meaney S, Lutjohann D, Diczfalusy U, Bjorkhem I. Formation of oxysterols from different pools of cholesterol as studied by stable isotope technique: cerebral origin of most circulating 24S-hydroxycholesterol in rats, but not in mice. Biochem Biophys Acta 2000; 1486: 293-8.
Vaya J, Schipper HM. Oxysterols, cholesterol homeostasis, and Alzheimer disease. J Neurochem 2007; 102: 1727-37.
Lathe R, Sapronova A, Kotelevtsev Y. Atherosclerosis and Alzheimer-diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 2014; 14: 36.
Marwarha G, Rhen T, Schommer T, Ghribi O. The oxysterol 27-hydroxycholesterol regulates alpha-synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors-relevance to Parkinson's disease. J Neurochem 2011; 119: 1119-36.
Bjorkhem I, Lovgren-Sandblom A, Leoni V et al. Oxysterols and Parkinson's disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease. Neurosci Lett 2013; 555: 102-5.
Teunissen CE, Dijkstra C, Polman C. Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol 2005; 4: 32-41.
Baek AE, Yu YA, He S et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun 2017; 8: 864.
Siam A, Brancale A, Simons C. Comparative modeling of 25-hydroxycholesterol-7alpha-hydroxylase (CYP7B1): ligand binding and analysis of hereditary spastic paraplegia type 5 CYP7B1 mutations. J Mol Model 2012; 18: 441-53.
Schols L, Rattay TW, Martus P et al. Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain 2017; 140: 3112-27.
Ismail MA, Mateos L, Maioli S et al. 27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation. J Exp Med 2017; 214: 699-717.
Mateos L, Akterin S, Gil-Bea FJ et al. Activity-regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro. Brain Pathol 2009; 19: 69-80.
Heverin M, Maioli S, Pham T et al. 27-hydroxycholesterol mediates negative effects of dietary cholesterol on cognition in mice. Behav Brain Res 2015; 278: 356-9.
Mateos L, Ismail M-A-M, Gil-Bea F-J et al. Side chain-oxidized oxysterols regulate the brain renin-angiotensin system through a liver X receptor-dependent mechanism. J Biol Chem 2011; 286: 25574-85.
Mateos L, Ismail MA, Gil-Bea FJ et al. Upregulation of brain renin angiotensin system by 27-hydroxycholesterol in Alzheimer's disease. J Alzheimers Dis 2011; 24: 669-79.
Meir K, Kitsberg D, Alkalay I et al. Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis. J Biol Chem 2002; 277: 34036-41.
Albiston AL, McDowall SG, Matsacos D et al. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem 2001; 276: 48623-6.
Mast N, Lin JB, Pikuleva IA. Marketed drugs can inhibit cytochrome P450 27A1, a potential new target for breast cancer adjuvant therapy. Mol Pharmacol 2015; 88: 428-36.
Marciniak E, Leboucher A, Caron E et al. Tau deletion promotes brain insulin resistance. J Exp Med 2017; 214: 2257-69.
Spolcova A, Mikulaskova B, Krskova K et al. Deficient hippocampal insulin signaling and augmented Tau phosphorylation is related to obesity- and age-induced peripheral insulin resistance: a study in Zucker rats. BMC Neurosci 2014; 15: 111.
Marwarha G, Dasari B, Prasanthi JR, Schommer J, Ghribi O. Leptin reduces the accumulation of Abeta and phosphorylated tau induced by 27-hydroxycholesterol in rabbit organotypic slices. J Alzheimers Dis 2010; 19: 1007-19.
Rahman A, Akterin S, Flores-Morales A et al. High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice. FEBS Lett 2005; 579: 6411-6.
LaFerla FM, Troncoso JC, Strickland DK, Kawas CH, Jay G. Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Abeta stabilization. J Clin Invest 1997; 100: 310-20.
Cummings BJ, Cotman CW. Image analysis of beta-amyloid load in Alzheimer's disease and relation to dementia severity. Lancet 1995; 346: 1524-8.
Kalaria RN, Cohen DL, Greenberg BD et al. Abundance of the longer A beta 42 in neocortical and cerebrovascular amyloid beta deposits in Swedish familial Alzheimer's disease and Down's syndrome. NeuroReport 1996; 7: 1377-81.
Mattsson N, Zetterberg H, Hansson O et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009; 302: 385-93.
Eckman CB, Mehta ND, Crook R et al. A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43). Hum Mol Genet 1997; 6: 2087-9.
Sandebring A, Welander H, Winblad B, Graff C, Tjernberg LO. The pathogenic abeta43 is enriched in familial and sporadic Alzheimer disease. PLoS ONE 2013; 8: e55847.
Sturchler-Pierrat C, Abramowski D, Duke M et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 1997; 94: 13287-92.
Holcomb L, Gordon MN, McGowan E et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 1998; 4: 97-100.
Games D, Adams D, Alessandrini R et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 1995; 373: 523-7.
Oddo S, Caccamo A, Shepherd JD et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003; 39: 409-21.
Golde TE, Dickson D, Hutton M. Filling the gaps in the abeta cascade hypothesis of Alzheimer's disease. Curr Alzheimer Res 2006; 3: 421-30.
Saito T, Matsuba Y, Yamazaki N, Hashimoto S, Saido TC. Calpain activation in Alzheimer's model mice is an artifact of APP and presenilin overexpression. J Neurosci 2016; 36: 9933-6.
Saito T, Matsuba Y, Mihira N et al. Single App knock-in mouse models of Alzheimer's disease. Nat Neurosci 2014; 17: 661-3.
Geula C, Nagykery N, Wu CK. Amyloid-beta deposits in the cerebral cortex of the aged common marmoset (Callithrix jacchus): incidence and chemical composition. Acta Neuropathol 2002; 103: 48-58.
Sasaguri H, Nilsson P, Hashimoto S et al. APP mouse models for Alzheimer's disease preclinical studies. EMBO J 2017; 36: 2473-87.
Castellano JM, Kim J, Stewart FR et al. Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci Transl Med 2011; 3: 89ra57.
Hardy J, Bogdanovic N, Winblad B et al. Pathways to Alzheimer's disease. J Intern Med 2014; 275: 296-303.
Hardy J. Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis 2006; 9: 151-3.
Harold D, Abraham R, Hollingworth P et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 2009; 41: 1088-93.
Jones B. Alzheimer disease: TREM2 linked to late-onset AD. Nat Rev Neurol 2013; 9: 5.
Forsberg A, Almkvist O, Engler H, Wall A, Langstrom B, Nordberg A. High PIB retention in Alzheimer's disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res 2010; 7: 56-66.
Klunk WE, Engler H, Nordberg A et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 2004; 55: 306-19.
Rodriguez-Vieitez E, Saint-Aubert L, Carter SF et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain 2016; 139: 922-36.
Aisen PS, Petersen RC, Donohue M, Weiner MW. Alzheimer's disease neuroimaging I. Alzheimer's disease neuroimaging initiative 2 clinical core: progress and plans. Alzheimers Dement 2015; 11: 734-9.
Aisen PS, Petersen RC, Donohue MC et al. Clinical core of the Alzheimer's disease neuroimaging initiative: progress and plans. Alzheimers Dement 2010; 6: 239-46.
Jack CR Jr, Bennett DA, Blennow K et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14: 535-62.
Forsberg A, Engler H, Almkvist O et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 2008; 29: 1456-65.
Budd Haeberlein S, O'Gorman J, Chiao P et al. Clinical development of aducanumab, an anti-abeta human monoclonal antibody being investigated for the treatment of early Alzheimer's disease. J Prev Alzheimers Dis 2017; 4: 255-63.
Honig LS, Vellas B, Woodward M et al. Trial of solanezumab for mild dementia due to Alzheimer's disease. N Engl J Med 2018; 378: 321-30.
Egan MF, Kost J, Tariot PN et al. Randomized trial of verubecestat for mild-to-moderate Alzheimer's disease. N Engl J Med 2018; 378: 1691-703.
Gulisano W, Maugeri D, Baltrons MA et al. Role of amyloid-beta and tau proteins in Alzheimer's disease: confuting the amyloid cascade. J Alzheimers Dis 2018; 64: S611-31.
Gold M. Phase II clinical trials of anti-amyloid beta antibodies: when is enough, enough? Alzheimers Dement (N Y) 2017; 3: 402-9.
Wisniewski T. Active immunotherapy for Alzheimer's disease. Lancet Neurol 2012; 11: 571-2.
Dodel RC, Hampel H, Du Y. Immunotherapy for Alzheimer's disease. Lancet Neurol 2003; 2: 215-20.
Sigurdsson EM, Scholtzova H, Mehta PD, Frangione B, Wisniewski T. Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. Am J Pathol 2001; 159: 439-47.
Morgan D. Immunotherapy for Alzheimer's disease. J Intern Med 2011; 269: 54-63.
Novak P, Schmidt R, Kontsekova E et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol 2017; 16: 123-34.
Novak P, Schmidt R, Kontsekova E et al. FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease. Alzheimers Res Ther 2018; 10: 108.
Logovinsky V, Satlin A, Lai R et al. Safety and tolerability of BAN2401-a clinical study in Alzheimer's disease with a protofibril selective Abeta antibody. Alzheimers Res Ther 2016; 8: 14.
Bard F, Barbour R, Cannon C et al. Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer's disease-like neuropathology. Proc Natl Acad Sci USA 2003; 100: 2023-8.
Lemere CA. Immunotherapy for Alzheimer's disease: hoops and hurdles. Mol Neurodegener 2013; 8: 36.
Panza F, Frisardi V, Imbimbo BP, Seripa D, Solfrizzi V, Pilotto A. Monoclonal antibodies against beta-amyloid (Abeta) for the treatment of Alzheimer's disease: the Abeta target at a crossroads. Expert Opin Biol Ther 2011; 11: 679-86.
Pfeifer M, Boncristiano S, Bondolfi L et al. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 2002; 298: 1379.
Crane A, Brubaker WD, Johansson JU et al. Peripheral complement interactions with amyloid beta peptide in Alzheimer's disease: 2. Relationship to amyloid beta immunotherapy. Alzheimers Dement 2018; 14: 243-52.
Cehlar O, Skrabana R, Revajova V, Novak M. Structural aspects of Alzheimer's disease immunotherapy targeted against amyloid-beta peptide. Bratisl Lek Listy 2018; 119: 201-4.
Bittar A, Sengupta U, Kayed R. Prospects for strain-specific immunotherapy in Alzheimer's disease and tauopathies. NPJ Vaccines 2018; 3: 9.
Wilcock DM, Rojiani A, Rosenthal A et al. Passive immunotherapy against Abeta in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J Neuroinflamm 2004; 1: 24.
Vandenberghe R, Riviere ME, Caputo A et al. Active Abeta immunotherapy CAD106 in Alzheimer's disease: a phase 2b study. Alzheimers Dement (N Y) 2017; 3: 10-22.
Orgogozo JM, Gilman S, Dartigues JF et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003; 61: 46-54.
Morgan D. Modulation of microglial activation state following passive immunization in amyloid depositing transgenic mice. Neurochem Int 2006; 49: 190-4.
Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 2010; 6: 108-19.
Farlow MR, Andreasen N, Riviere ME et al. Long-term treatment with active Abeta immunotherapy with CAD106 in mild Alzheimer's disease. Alzheimers Res Ther 2015; 7: 23.
Winblad B, Andreasen N, Minthon L et al. Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol 2012; 11: 597-604.
Winblad B, Graf A, Riviere ME, Andreasen N, Ryan JM. Active immunotherapy options for Alzheimer's disease. Alzheimers Res Ther 2014; 6: 7.
Menendez-Gonzalez M, Perez-Pinera P, Martinez-Rivera M, Muniz AL, Vega JA. Immunotherapy for Alzheimer's disease: rational basis in ongoing clinical trials. Curr Pharm Des 2011; 17: 508-20.
Wiessner C, Wiederhold KH, Tissot AC et al. The second-generation active Abeta immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 2011; 31: 9323-31.
Sevigny J, Chiao P, Bussiere T et al. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature 2016; 537: 50-6.
Sevigny J, Chiao P, Bussiere T et al. Addendum: The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature 2017; 546: 564.
Piazza F. Reader response: a phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology 2018; 90: 144-5.
Relkin NR, Thomas RG, Rissman RA et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology 2017; 88: 1768-75.
Eriksson CA. BioArctic Announces Positive Topline Results of BAN2401 Phase 2b at 18 months in Early Alzheimer's Disease. BioArctic.se: BioArctic, 2018.
Nilsson P, Loganathan K, Sekiguchi M et al. Abeta secretion and plaque formation depend on autophagy. Cell Rep 2013; 5: 61-9.
Caspersen C, Wang N, Yao J et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J 2005; 19: 2040-1.
Sanchez-Pulido L, Devos D, Valencia A. BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends Biochem Sci 2002; 27: 329-32.
Hermansson E, Schultz S, Crowther D et al. The chaperone domain BRICHOS prevents CNS toxicity of amyloid-beta peptide in Drosophila melanogaster. Dis Model Mech 2014; 7: 659-65.
Kim J, Chakrabarty P, Hanna A et al. Normal cognition in transgenic BRI2-Abeta mice. Mol Neurodegener 2013; 8: 15.
Willander H, Askarieh G, Landreh M et al. High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C. Proc Natl Acad Sci USA 2012; 109: 2325-9.
Walther FJ, Hernandez-Juviel JM, Waring AJ. Aerosol delivery of synthetic lung surfactant. PeerJ 2014; 2: e403.
Leinenga G, Gotz J. Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer's disease mouse model. Sci Transl Med 2015; 7: 278ra33.
Bray N. Biologics: transferrin’ bispecific antibodies across the blood-brain barrier. Nat Rev Drug Discov 2015; 14: 14-5.
Friden PM, Walus LR, Musso GF, Taylor MA, Malfroy B, Starzyk RM. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proc Natl Acad Sci USA 1991; 88: 4771-5.
Okun I, Tkachenko SE, Khvat A, Mitkin O, Kazey V, Ivachtchenko AV. From anti-allergic to anti-Alzheimer's: molecular pharmacology of dimebon. Curr Alzheimer Res 2010; 7: 97-112.
Doody RS, Gavrilova SI, Sano M et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet 2008; 372: 207-15.
Grigorev VV, Dranyi OA, Bachurin SO. Comparative study of action mechanisms of dimebon and memantine on AMPA- and NMDA-subtypes glutamate receptors in rat cerebral neurons. Bull Exp Biol Med 2003; 136: 474-7.
DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 2001; 98: 8850-5.
He Z, Guo JL, McBride JD et al. Amyloid-beta plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 2018; 24: 29-38.
Ando K, Brion JP, Stygelbout V et al. Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer's brains. Acta Neuropathol 2013; 125: 861-78.
Chapuis J, Hansmannel F, Gistelinck M et al. Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol Psychiatry 2013; 18: 1225-34.
Dourlen P, Fernandez-Gomez FJ, Dupont C et al. Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology. Mol Psychiatry 2017; 22: 874-83.
Moreau K, Fleming A, Imarisio S et al. PICALM modulates autophagy activity and tau accumulation. Nat Commun 2014; 5: 4998.
Goedert M, Spillantini MG, Cairns NJ, Crowther RA. Tau proteins of alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 1992; 8: 159-68.
Tolnay M, Sergeant N, Ghestem A et al. Argyrophilic grain disease and Alzheimer's disease are distinguished by their different distribution of tau protein isoforms. Acta Neuropathol 2002; 104: 425-34.
Hof PR, Delacourte A, Bouras C. Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. Acta Neuropathol 1992; 84: 45-51.
Hof PR, Knabe R, Bovier P, Bouras C. Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol 1991; 82: 321-6.
Schmidt ML, Zhukareva V, Newell KL, Lee VM, Trojanowski JQ. Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease. Acta Neuropathol 2001; 101: 518-24.
Buée-Scherrer V, Buée L, Leveugle B et al. Pathological τ proteins in postencephalitic parkinsonism: comparison with Alzheimer's disease and other neurodegenerative disorders. Ann Neurol 1997; 42: 356-9.
Ikeda K, Akiyama H, Kondo H et al. Thorn-shaped astrocytes: possibly secondarily induced tau-positive glial fibrillary tangles. Acta Neuropathol 1995; 90: 620-5.
Caparros E. Avant-propos. Revue générale de droit 2002; 32: 205.
Caparros-Lefebvre D, Golbe LI, Deramecourt V et al. A geographical cluster of progressive supranuclear palsy in northern France. Neurology 2015; 85: 1293-300.
Buée-Scherrer V, Buée L, Hof PR et al. Tau variants in aging and neurodegenerative disorders. K.A. Jellinger Alzheimer's Disease: Lessons from Cell Biology. Berlin and Heidelberg: Springer, 1995; 132-49.
Buée-Scherrer V, Hof PR, Buée L et al. Hyperphosphorylated tau proteins differentiate corticobasal degeneration and Pick's disease. Acta Neuropathol 1996; 91: 351-9.
Mailliot C, Sergeant N, Bussière T, Caillet-Boudin M-L, Delacourte A, Buée L. Phosphorylation of specific sets of tau isoforms reflects different neurofibrillary degeneration processes. FEBS Lett 1998; 433: 201-4.
Delacourte A, Robitaille Y, Sergeant N et al. Specific pathological tau protein variants characterize pickʼs disease. J Neuropathol Exp Neurol 1996; 55: 159-68.
Delacourte A, Sergeant N, Wattez A, Gauvreau D, Robitaille Y. Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their? Isoform distribution and phosphorylation. Ann Neurol 1998; 43: 193-204.
Love S, Bridges LR, Case CP. Neurofibrillary tangles in Niemann-Pick disease type C. Brain 1995; 118: 119-29.
Spillantini MG, Tolnay M, Love S, Goedert M. Microtubule-associated protein tau, heparan sulphate and alpha-synuclein in several neurodegenerative diseases with dementia. Acta Neuropathol 1999; 97: 585-94.
Sergeant N, Sablonniere B, Schraen-Maschke S et al. Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1. Hum Mol Genet 2001; 10: 2143-55.
Vermersch P, Sergeant N, Ruchoux MM et al. Specific tau variants in the brains of patients with myotonic dystrophy. Neurology 1996; 47: 711-7.
Goedert M, Ghetti B, Spillantini MG. Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: a006254.
Smith PY, Delay C, Girard J et al. MicroRNA-132 loss is associated with tau exon 10 inclusion in progressive supranuclear palsy. Hum Mol Genet 2011; 20: 4016-24.
Baker M, Litvan I, Houlden H et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999; 8: 711-5.
Jucker M, Walker LC. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol 2011; 70: 532-40.
Kuchibhotla KV, Wegmann S, Kopeikina KJ et al. Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo. Proc Natl Acad Sci USA 2014; 111: 510-4.
Ahmed T, Van der Jeugd A, Blum D et al. Cognition and hippocampal synaptic plasticity in mice with a homozygous tau deletion. Neurobiol Aging 2014; 35: 2474-8.
Santacruz K, Lewis J, Spires T et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005; 309: 476-81.
Sydow A, Van der Jeugd A, Zheng F et al. Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 2011; 31: 2511-25.
Pooler AM, Usardi A, Evans CJ, Philpott KL, Noble W, Hanger DP. Dynamic association of tau with neuronal membranes is regulated by phosphorylation. Neurobiol Aging 2012; 33: 431 e27-38.
Frost B, Hemberg M, Lewis J, Feany MB. Tau promotes neurodegeneration through global chromatin relaxation. Nat Neurosci 2014; 17: 357-66.
Reynolds CH, Garwood CJ, Wray S et al. Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases. J Biol Chem 2008; 283: 18177-86.
Ittner LM, Ke YD, Delerue F et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 2010; 142: 387-97.
Sperling RA, Aisen PS, Beckett LA et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 280-92.
Marengoni A, Rizzuto D, Fratiglioni L et al. The effect of a 2-year intervention consisting of diet, physical exercise, cognitive training, and monitoring of vascular risk on chronic morbidity-the FINGER randomized controlled trial. J Am Med Dir Assoc 2018; 19: 355-60 e1.
Medina M, Khachaturian ZS, Rossor M, Avila J, Cedazo-Minguez A. Toward common mechanisms for risk factors in Alzheimer's syndrome. Alzheimers Dement (N Y) 2017; 3: 571-8.
Vanitallie TB. Preclinical sporadic Alzheimer's disease: target for personalized diagnosis and preventive intervention. Metabolism 2013; 62(Suppl. 1): S30-3.
Silvestre FJ, Lauritano D, Carinci F, Silvestre-Rangil J, Martinez-Herrera M, Del Olmo A. Neuroinflammation, Alzheimers disease and periodontal disease: is there an association between the two processes? J Biol Regul Homeost Agents 2017; 31: 189-96.
Rafii MS, Tuszynski MH, Thomas RG et al. Adeno-associated viral vector (serotype 2)-nerve growth factor for patients with Alzheimer disease: a randomized clinical trial. JAMA Neurol 2018; 75: 834-41.
Khachaturian AS, Hayden KM, Mielke MM et al. Future prospects and challenges for Alzheimer's disease drug development in the era of the NIA-AA research framework. Alzheimers Dement 2018; 14: 532-4.
Kodamullil AT, Zekri F, Sood M et al. Trial watch: tracing investment in drug development for Alzheimer disease. Nat Rev Drug Discov 2017; 16: 819.
Khachaturian ZS, Mesulam MM, Khachaturian AS, Mohs RC. The special topics section of Alzheimer's & Dementia. Alzheimers Dement 2015; 11: 1261-4.
Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat Med 2018; 24: 927-30.
Yamamoto N, Fujii Y, Kasahara R et al. Simvastatin and atorvastatin facilitates amyloid beta-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways. Glia 2016; 64: 952-62.
Janson CG. Diverse effects of statins in Alzheimer's disease. Sci Transl Med 2016; 8: 330ec44-ec44.
Salta E, De Strooper B. microRNA-132: a key noncoding RNA operating in the cellular phase of Alzheimer's disease. FASEB J 2017; 31: 424-33.
Chaudhuri AD, Dastgheyb RM, Yoo SW et al. TNFalpha and IL-1beta modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis 2018; 9: 363.
Martin R, Bajo-Graneras R, Moratalla R, Perea G, Araque A. Circuit-specific signaling in astrocyte-neuron networks in basal ganglia pathways. Science 2015; 349: 730-4.
Parikshak NN, Gandal MJ, Geschwind DH. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders. Nat Rev Genet 2015; 16: 441-58.
Colonna M, Wang Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci 2016; 17: 201-7.
Donath MY, Dalmas E, Sauter NS, Boni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab 2013; 17: 860-72.
Iaccarino HF, Singer AC, Martorell AJ et al. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 2016; 540: 230-5.
Deeks SG, Lewin SR, Ross AL et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat Med 2016; 22: 839-50.
Hodge JW, Ardiani A, Farsaci B, Kwilas AR, Gameiro SR. The tipping point for combination therapy: cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors. Semin Oncol 2012; 39: 323-39.
LoRusso PM, Canetta R, Wagner JA et al. Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop. Clin Cancer Res 2012; 18: 6101-9.
Tumbarello M, Viale P, Viscoli C et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis 2012; 55: 943-50.
Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 2011; 10: 819-28.
Sink KM, Leng X, Williamson J et al. Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study. Arch Intern Med 2009; 169: 1195-202.