NGF and the Amyloid Precursor Protein in Alzheimer's Disease: From Molecular Players to Neuronal Circuits.
APP processing
APP/NGF signalling interplay
Cholinergic circuit pathology
NGF
Neuronal insulin resistance
Neurotrophins
TrkA
miRNA
p75NTR
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
1
9
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD), one of the most common causes of dementia in elderly people, is characterized by progressive impairment in cognitive function, early degeneration of basal forebrain cholinergic neurons (BFCNs), abnormal metabolism of the amyloid precursor protein (APP), amyloid beta-peptide (Aβ) depositions, and neurofibrillary tangles. According to the cholinergic hypothesis, dysfunction of acetylcholine-containing neurons in the basal forebrain contributes markedly to the cognitive decline observed in AD. In addition, the neurotrophic factor hypothesis posits that the loss nerve growth factor (NGF) signalling in AD may account for the vulnerability to atrophy of BFCNs and consequent impairment of cholinergic functions. Though acetylcholinesterase inhibitors provide only partial and symptomatic relief to AD patients, emerging data from in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) studies in mild cognitive impairment (MCI) and AD patients highlight the early involvement of BFCNs in MCI and the early phase of AD. These data support the cholinergic and neurotrophic hypotheses of AD and suggest new targets for AD therapy.Different mechanisms account for selective vulnerability of BFCNs to AD pathology, with regard to altered metabolism of APP and tau. In this review, we provide a general overview of the current knowledge of NGF and APP interplay, focusing on the role of APP in regulating NGF receptors trafficking/signalling and on the involvement of NGF in modulating phosphorylation of APP, which in turn controls APP intracellular trafficking and processing. Moreover, we highlight the consequences of APP interaction with p75NTR and TrkA receptor, which share the same binding site within the APP juxta-membrane domain. We underline the importance of insulin dysmetabolism in AD pathology, in the light of our recent data showing that overlapping intracellular signalling pathways stimulated by NGF or insulin can be compensatory. In particular, NGF-based signalling is able to ameliorates deficiencies in insulin signalling in the medial septum of 3×Tg-AD mice. Finally, we present an overview of NGF-regulated microRNAs (miRNAs). These small non-coding RNAs are involved in post-transcriptional regulation of gene expression , and we focus on a subset that are specifically deregulated in AD and thus potentially contribute to its pathology.
Identifiants
pubmed: 34453297
doi: 10.1007/978-3-030-74046-7_10
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-165Informations de copyright
© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
Allen SJ, Watson JJ, Dawbarn D (2011) The neurotrophins and their role in Alzheimer’s disease. Curr Neuropharmacol 9:559–573
pubmed: 22654716
pmcid: 3263452
doi: 10.2174/157015911798376190
Amakiri N, Kubosumi A, Tran J, Reddy PH (2019) Amyloid beta and microRNAs in Alzheimer’s disease. Front Neurosci 13:430
pubmed: 31130840
pmcid: 6510214
doi: 10.3389/fnins.2019.00430
Appel SH (1981) A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 10:499–505
pubmed: 6173010
doi: 10.1002/ana.410100602
Arnold SE, Arvanitakis Z, Macauley-Rambach SL et al (2018) Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol 14:168–181
pubmed: 29377010
pmcid: 6098968
doi: 10.1038/nrneurol.2017.185
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42(3 Pt 1):631–639
pubmed: 1549228
doi: 10.1212/WNL.42.3.631
Baker-Nigh A, Vahedi S, Davis EG, Weintraub S, Bigio EH, Klein WL, Geula C (2015) Neuronal amyloid-β accumulation within cholinergic basal forebrain in ageing and Alzheimer’s disease. Brain 138:1722–1737
pubmed: 25732182
pmcid: 4542619
doi: 10.1093/brain/awv024
Ballinger EC, Ananth M, Talmage DA, Role LW (2016) Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 91:1199–1218
pubmed: 27657448
pmcid: 5036520
doi: 10.1016/j.neuron.2016.09.006
Barbagallo AP, Weldon R, Tamayev R, Zhou D, Giliberto L, Foreman O, D’Adamio L (2010) Tyr(682) in the intracellular domain of APP regulates amyloidogenic APP processing in vivo. PLoS One 5(11):e15503
pubmed: 21103325
pmcid: 2982846
doi: 10.1371/journal.pone.0015503
Barbato C, Giacovazzo G, Albiero F, Scardigli R, Scopa C, Ciotti MT, Strimpakos G, Coccurello R, Ruberti F (2020) Cognitive decline and modulation of Alzheimer’s disease-related genes after inhibition of microRNA-101 in mouse hippocampal neurons. Mol Neurobiol 57(7):3183–3194
pubmed: 32504417
doi: 10.1007/s12035-020-01957-8
Batarseh YS, Duong QV, Mousa YM, Al Rihani SB, Elfakhri K, Kaddoumi A (2016) Amyloid-beta and astrocytes interplay in amyloid-beta related disorders. Int J Mol Sci 17:338
pubmed: 26959008
pmcid: 4813200
doi: 10.3390/ijms17030338
Bejanin A, Schonhaut DR, La Joie R, Krame JH, Baker SL, Sosa N et al (2017) Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease. Brain 140:3286–3300
pubmed: 29053874
pmcid: 5841139
doi: 10.1093/brain/awx243
Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, Perl DP, Schmeidler J, Kanof P, Davis KL (1995) Neurochemical correlates of dementia severity in Alzheimer’s disease: relative importance of the cholinergic deficits. J Neurochem 64:749–760
pubmed: 7830069
doi: 10.1046/j.1471-4159.1995.64020749.x
Bilousova T, Miller CA, Poon WW, Vinters HV, Corrada M, Kawas C, Hayden EY, Teplow DB, Glabe C, Albay R 3rd, Cole GM, Teng E, Gylys KH (2016) Synaptic amyloid-beta oligomers precede p-Tau and differentiate high pathology control cases. Am J Pathol 186:185–198
pubmed: 26718979
pmcid: 4715217
doi: 10.1016/j.ajpath.2015.09.018
Botté A, Lainé J, Xicota L, Heiligenstein X, Fontaine G, Kasri A, Rivals I, Goh P, Faklaris O, Cossec JC, Morel E, Rebillat AS, Nizetic D, Raposo G, Potier MC (2020) Ultrastructural and dynamic studies of the endosomal compartment in Down syndrome. Acta Neuropathol Commun 8(1):89
pubmed: 32580751
pmcid: 7315513
doi: 10.1186/s40478-020-00956-z
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
pubmed: 1759558
doi: 10.1007/BF00308809
Calissano P, Amadoro G, Matrone C, Ciaffrè S, Corsetti V, Marolda R, Ciotti MT, DiLuzio A, Severini C, Mercanti D, Provenzano C, Canu N (2010) Does the term “NGF” actually means anti-amyloidogenic ? The case of NGF. Cell Death Diff 17(7):1126–1133
doi: 10.1038/cdd.2010.38
Cantero JL, Zaborszky L, Atienza M (2016) Volume loss of the nucleus basalis of meynert is associated with atrophy of innervated regions in mild cognitive impairment. Cereb Cortex 27(8):3881–3889
pmcid: 6059249
pubmed: 6059249
Canu N, Pagano I, LaRosa LR, Pellegrino M, Ciotti MT, Mercanti D, Moretti F, Sposato V, Triaca V, Petrella C, Maruyama IN, Levi A, Calissano P (2017a) Association of TrkA and APP is promoted by NGF and reduced by cell death-promoting agents. Front Mol Neurosci 10:15
pubmed: 28197073
pmcid: 5281621
doi: 10.3389/fnmol.2017.00015
Canu N, Amadoro G, Triaca V, Latina V, Sposato V, Corsetti V, Severini C, Ciotti MT, Calissano P (2017b) The intersection of NGF/TrkA signaling and amyloid precursor protein processing in Alzheimer’s disease neuropathology. Int J Mol Sci 18(6):1319
pmcid: 5486140
doi: 10.3390/ijms18061319
pubmed: 5486140
Caporaso GL, Takei K, Gandy SE, Matteoli M, Mundigl O, Greengard P, De Camilli P (1994) Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein. Neurosci 14:3122–3138
doi: 10.1523/JNEUROSCI.14-05-03122.1994
Capsoni S, Ugolini G, Comparini A, Ruberti F, Berardi N, Cattaneo A (2000) Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice. Proc Natl Acad Sci USA 97:6826–6831
pubmed: 10841577
pmcid: 18754
doi: 10.1073/pnas.97.12.6826
Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, Mehta PD, Buxbaum J, Haroutunian V, Nixon RA (2004) Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and Down syndrome. Neurobiol Aging 25:1263–1272
pubmed: 15465622
doi: 10.1016/j.neurobiolaging.2004.02.027
Chang KA, Kim HS, Ha TY, Ha JW, Shin KY, Jeong YH, Lee JP, Park CH, Kim S, Baik TK, Suh YH (2006) Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Mol Cell Biol 26:4327–4338
pubmed: 16705182
pmcid: 1489099
doi: 10.1128/MCB.02393-05
Chatterjee N, Sanphui P, Kemeny S, Greene LA, Biswas SC (2016) Role and regulation of Cdc25A phosphatase in neuron death induced by NGF deprivation or β-amyloid. Cell Death Discov 2:16083
pubmed: 28028440
pmcid: 5149581
doi: 10.1038/cddiscovery.2016.83
Chen X-Q, Mobley WC (2019) Exploring the pathogenesis of Alzheimer disease in basal forebrain cholinergic neurons: converging insights from alternative hypotheses. Front Neurosci 13:446
pubmed: 31133787
pmcid: 6514132
doi: 10.3389/fnins.2019.00446
Chen Q, Sawa M, Mobley WC (2018) Dysregulation of neurotrophin signaling in the pathogenesis of Alzheimer disease and of Alzheimer disease in Down syndrome. Free Radic Biol Med 114:52–61
pubmed: 29031834
doi: 10.1016/j.freeradbiomed.2017.10.341
Chow H-M, Shi M, Cheng A, Gao Y, Chen G, Song X, So RWL, Zhang J, Herrup K (2019) Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence. Nat Neurosci 22:1806–1819
pubmed: 31636448
doi: 10.1038/s41593-019-0505-1
Chung CG, Lee H, Lee SB (2018) Mechanisms of protein toxicity in neurodegenerative diseases. Cell Mol Life Sci 75:3159–3180
pubmed: 29947927
pmcid: 6063327
doi: 10.1007/s00018-018-2854-4
Cline EN, Bicca MA, Viola KL, Klein WL (2018) The amyloid-β oligomer hypothesis: beginning of the third decade. J Alzheimer Dis 64(S1):S567–S610
doi: 10.3233/JAD-179941
Colom LV, García-Hernández A, Castañeda MT, Perez-Cordova MG, Garrido-Sanabria ER (2006) Septo-hippocampal networks in chronically epileptic rats: potential antiepileptic effects of theta rhythm generation. J Neurophysiol 95:3645–3653
pubmed: 16554504
doi: 10.1152/jn.00040.2006
pmcid: 16554504
Craft S (2007) Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 4(2):147–152
pubmed: 17430239
doi: 10.2174/156720507780362137
pmcid: 17430239
Cuello AC, Bruno MA, Bell KFS (2007) NGF-cholinergic dependency in brain aging, MCI and Alzheimer’s disease. Curr Alzheimer Res 4:351–358
pubmed: 17908036
doi: 10.2174/156720507781788774
pmcid: 17908036
Cui GH, Wu J, Mou FF, Xie WH, Wang FB, Wang QL, Fang J, Xu YW, Dong YR, Liu JR, Guo HD (2018) Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice. FASEB J 32(2):654–668
pubmed: 28970251
doi: 10.1096/fj.201700600R
pmcid: 28970251
Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2:1403
pubmed: 63862
doi: 10.1016/S0140-6736(76)91936-X
De Felice FG (2013) Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 123:531–539
pubmed: 23485579
pmcid: 3561831
doi: 10.1172/JCI64595
De Felice FG, Lourenco MV, Ferreira ST (2014) How does brain insulin resistance develop in Alzheimer’s disease? Alzheimer Dement 10:S26–S32
doi: 10.1016/j.jalz.2013.12.004
de la Monte SM (2012) Brain insulin resistance and deficiency as therapeutic targets in Alzheimers disease. Curr Alzheimer Res 9(1):35–66
pubmed: 22329651
pmcid: 3349985
doi: 10.2174/156720512799015037
De Strooper B, Karran E (2016) The cellular phase of Alzheimer’s disease. Cell 164:603–615
pubmed: 26871627
doi: 10.1016/j.cell.2015.12.056
pmcid: 26871627
Dorszewska J, Prendecki M, Oczkowska A, Dezor M, Kozubski W (2016) Molecular basis of familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 13:952–963
pubmed: 26971934
pmcid: 26971934
doi: 10.2174/1567205013666160314150501
Ebenau JL, Timmers T, Wesselman LMP et al (2020) ATN classification and clinical progression in subjective cognitive decline. Neurology 95:e46–e58
pubmed: 32522798
pmcid: 7371376
doi: 10.1212/WNL.0000000000009724
Eggert S, Thomas C, Kins S, Hermey G (2018) Trafficking in Alzheimer’s disease: modulation of APP transport and processing by the transmembrane proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin. Mol Neurobiol 55(7):5809–5829
pubmed: 29079999
doi: 10.1007/s12035-017-0806-x
El-Shimy IA, Heikal OA, Hamdi N (2015) Minocycline attenuates Abeta oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing Abeta fibrils phagocytosis. Neurosci Lett 609:36–41
pubmed: 26472705
doi: 10.1016/j.neulet.2015.10.024
pmcid: 26472705
Exalto LG, Biessels GJ, Karter AJ, Huang ES, Katon WJ, Minkoff JR, Whitmer RA (2013) Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study. Lancet Diabetes Endocrinol 1:183–190
pubmed: 24622366
pmcid: 4429783
doi: 10.1016/S2213-8587(13)70048-2
Ferreira LSS, Fernandes CS, Vieira MNN, de Felice FG (2018) Insulin resistance in Alzheimer’s disease. Front Neurosci 12:830
pubmed: 30542257
pmcid: 6277874
doi: 10.3389/fnins.2018.00830
Fisher A (2012) Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer’s disease. J Neurochem 120(Suppl 1):22–33
pubmed: 22122190
doi: 10.1111/j.1471-4159.2011.07507.x
pmcid: 22122190
Fishwick KJ, Rylett RJ (2015) Insulin regulates the activity of the high-affinity choline transporter CHT. PLoS One 10:e0132934
pubmed: 26161852
pmcid: 4498808
doi: 10.1371/journal.pone.0132934
Fombonne J, Rabizadeh S, Banwait S, Mehlen P, Bredesen DE (2009) Selective vulnerability in Alzheimer’s disease: amyloid precursor protein and p75(NTR) interaction. Ann Neurol 65(3):294–303
pubmed: 19334058
pmcid: 3057030
doi: 10.1002/ana.21578
Frost B, Jacks RL, Diamond MI (2009) Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 284:12845–12852
pubmed: 19282288
pmcid: 2676015
doi: 10.1074/jbc.M808759200
Geula C, Nagykery N, Nicholas A, Wu C-K (2008) Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. J Neuropathol Exp Neurol 67:309–318
pubmed: 18379437
doi: 10.1097/NEN.0b013e31816a1df3
pmcid: 18379437
Giannakopoulos P, Herrmann FR, Bussière T, Bouras C, Kövari E, Perl DP, Morrison JH, Gold G, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology 60:1495–1500
pubmed: 12743238
doi: 10.1212/01.WNL.0000063311.58879.01
pmcid: 12743238
Giuffrida ML, Caraci F, Pignataro B, Cataldo S, De Bona P, Bruno V, Molinaro G, Pappalardo G, Messina A, Palmigiano A, Garozzo D, Nicoletti F, Rizzarelli E, Copani A (2009) Beta-amyloid monomers are neuroprotective. J Neurosci 29:10582–10587
pubmed: 19710311
pmcid: 6665714
doi: 10.1523/JNEUROSCI.1736-09.2009
Goedert M, Spillantini MG, Cairns NJ, Crowther RA (1992) Tau proteins of alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8:159–168
pubmed: 1530909
doi: 10.1016/0896-6273(92)90117-V
pmcid: 1530909
Grothe M, Zaborszky L, Atienza M, Gil-Neciga E, Rodriguez-Romero R, Teipel SJ, Amunts K, Suarez-Gonzalez A, Cantero JL (2010) Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high risk of developing Alzheimer’s disease. Cereb Cortex 20:1685–1695
pubmed: 19889714
doi: 10.1093/cercor/bhp232
pmcid: 19889714
Guo JP, Arai T, Miklossy J, McGeer PL (2006) Aβ and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer’s disease. Proc Natl Acad Sci USA 103:1953–1958
pubmed: 16446437
pmcid: 1413647
doi: 10.1073/pnas.0509386103
Gustafsen C, Glerup S, Pallesen LT, Olsen D, Andersen OM, Nykjær A, Madsen P, Petersen CM (2013) Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. J Neurosci 33:64–71
pubmed: 23283322
pmcid: 6618638
doi: 10.1523/JNEUROSCI.2371-12.2013
Haass C, Kaether C, Thinakaran G, Sisodia S (2012) Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2(5):a006270
pubmed: 22553493
pmcid: 3331683
doi: 10.1101/cshperspect.a006270
Hamada N, Fujita Y, Kojima T, Kitamoto A, Akao Y, Nozawa Y, Ito M (2012) MicroRNA expression profiling of NGF-treated PC12 cells revealed a critical role for miR-221 in neuronal differentiation. Neurochem Int 60:743–750
pubmed: 22465943
doi: 10.1016/j.neuint.2012.03.010
pmcid: 22465943
Hangya B, Ranade SP, Lorenc M, Kepecs A (2015) Central cholinergic neurons are rapidly recruited by reinforcement feedback. Cell 162:1155–1168
pubmed: 26317475
pmcid: 26317475
doi: 10.1016/j.cell.2015.07.057
Hardy JA, Higgings GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185
pubmed: 1566067
doi: 10.1126/science.1566067
pmcid: 1566067
Heese K, Inoue N, Sawada T (2004) APP, NGF & the ‘Sunday-driver’ in a Trolley on the Road. Resto Neurol Neurosci 22(2):131–136
Hu YB, Ren RJ, Zhang YF, Huang Y, Cui HL, Ma C, Qiu WY, Wang H, Cui PJ, Chen HZ, Wang G (2019) Rho-associated coiled-coil kinase 1 activation mediates amyloid precursor protein site-specific Ser655 phosphorylation and triggers amyloid pathology. Aging Cell 18(5):e13001
pubmed: 31287605
pmcid: 6718535
doi: 10.1111/acel.13001
Improta-Caria AC, Nonaka CKV, Cavalcante BRR, De Sousa RAL, Aras Júnior R, Souza BSF (2020) Modulation of microRNAs as a potential molecular mechanism involved in the beneficial actions of physical exercise in Alzheimer disease. Int J Mol Sci 21(14):4977
pmcid: 7403962
doi: 10.3390/ijms21144977
Ioannou MS, Fahnestock M (2017) ProNGF, but Not NGF, switches from neurotrophic to apoptotic activity in response to reductions in TrkA receptor levels. Int J Mol Sci 18:599
pmcid: 5372615
doi: 10.3390/ijms18030599
Iqbal K, Liu F, Gong CX (2016) Tau and neurodegenerative disease: the story so far. Nat Rev Neurol 12(1):15–27
pubmed: 26635213
doi: 10.1038/nrneurol.2015.225
pmcid: 26635213
Irmady K, Jackman KA, Padow VA, Shahani N, Martin LA, Cerchietti L, Unsicker K, Iadecola C, Hempstead BL (2014) Mir-592 regulates the induction and cell death-promoting activity of p75NTR in neuronal ischemic injury. J Neurosci 34:3419–3428
pubmed: 24573298
pmcid: 3935094
doi: 10.1523/JNEUROSCI.1982-13.2014
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Contributors (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimerd Dement 14(4):535–562
doi: 10.1016/j.jalz.2018.02.018
Jeong DU, Lee JE, Lee SE, Chang WS, Kim SJ, Chang JW (2014) Improvements in memory after medial septum stimulation are associated with changes in hippocampal cholinergic activity and neurogenesis. BioMed Res Int 2014:1–10
Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414(6864):643–648
pubmed: 11740561
doi: 10.1038/414643a
pmcid: 11740561
Kashyap G, Bapat D, Das D, Gowaikar R, Amritkar RE, Rangarajan G, Ravindranath V, Ambika G (2019) Synapse loss and progress of Alzheimer’s disease—a network model. Sci Rep 9:6555
pubmed: 31024073
pmcid: 6484103
doi: 10.1038/s41598-019-43076-y
Kellar D, Craft S (2020) Brain insulin resistance in Alzheimer’s disease and related disorders: mechanisms and therapeutic approaches. Lancet Neurol 19:758–766
pubmed: 32730766
doi: 10.1016/S1474-4422(20)30231-3
pmcid: 32730766
Kerbler GM, Fripp J, Rowe CC, Villemagne VL, Salvado O, Rose S, Coulson EJ (2015) Basal forebrain atrophy correlates with amyloid β burden in Alzheimer’s disease. NeuroImage Clin 7:105–113
pubmed: 25610772
doi: 10.1016/j.nicl.2014.11.015
pmcid: 25610772
Kilimann I, Grothe M, Heinsen H, Alho EJ, Grinberg L, Amaro E Jr, Dos Santos GA, da Silva RE, Mitchell AJ, Frisoni GB, Bokde AL, Fellgiebel A, Filippi M, Hampel H, Klöppel S, Teipel SJ (2014) Subregional basal forebrain atrophy in Alzheimer’s disease: a multicenter study. J Alzheimers Dis 40:687–700
pubmed: 24503619
pmcid: 4120953
doi: 10.3233/JAD-132345
Kiltschewskij D, Cairns MJ (2019) Temporospatial guidance of activity-dependent gene expression by microRNA: mechanisms and functional implications for neural plasticity. Nucleic Acids Res 47:533–545
pubmed: 30535081
doi: 10.1093/nar/gky1235
Kitchigina VF (2018) Alterations of coherent theta and gamma network oscillations as an early biomarker of temporal lobe epilepsy and Alzheimer’s disease. Front Integr Neurosci 12:36
Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 269:17386–17389
pubmed: 8021238
doi: 10.1016/S0021-9258(17)32449-3
La Rosa LR, Perrone L, Nielsen MS, Calissano P, Andersen OM, Matrone C (2015) Y682G mutation of amyloid precursor protein promotes endo-lysosomal dysfunction by disrupting APP-SorLA interaction. Front Cell Neurosci 9:109
Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, Neve R, Ahlijanian MK, Tsai LH (2003) APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 163:83–95
pubmed: 14557249
pmcid: 2173445
doi: 10.1083/jcb.200301115
Leung LS, Ma J (2018) Medial septum modulates hippocampal gamma activity and prepulse inhibition in an N-methyl-d-aspartate receptor antagonist model of schizophrenia. Schizoph Res 198:36–44
doi: 10.1016/j.schres.2017.07.053
Li S, Wang X, Gu Y, Chen C, Wang Y, Liu J, Hu W, Yu B, Wang Y, Ding F, Liu Y, Gu X (2015) Let-7 microRNAs regenerate peripheral nerve regeneration by targeting nerve growth factor. Mol Ther 23(3):423–433
pubmed: 25394845
doi: 10.1038/mt.2014.220
pmcid: 25394845
Liu Y, Zhang YW, Wang X, Zhang H, You X, Liao FF, Xu HJ (2009) Intracellular trafficking of presenilin 1 is regulated by beta-amyloid precursor protein and phospholipase D1. Biol Chem 284:12145–12152
doi: 10.1074/jbc.M808497200
Mankin EA, Fried I (2020) Modulation of human memory by deep brain stimulation of the entorhinal-hippocampal circuitry. Neuron 106(2):218–235
pubmed: 32325058
pmcid: 7347298
doi: 10.1016/j.neuron.2020.02.024
Matrone C, Ciotti MT, Mercanti D, Marolda R, Calissano P (2008) NGF and BDNF signaling control amyloidogenic route and a production in hippocampal neurons. Proc Natl Acad Sci USA 105:13139–13144
pubmed: 18728191
pmcid: 2525562
doi: 10.1073/pnas.0806133105
Matrone C, Marolda R, Ciafrè S, Ciotti MT, Mercanti D, Calissano P (2009) Tyrosine kinase nerve growth factor receptor switches from prosurvival to proapoptotic activity via Abeta-mediated phosphorylation. Proc Natl Acad Sci U S A 106(27):11358–11363
pubmed: 19549834
pmcid: 2699376
doi: 10.1073/pnas.0904998106
Matrone C, Barbagallo AP, La Rosa LR, Florenzano F, Ciotti MT, Mercanti D, Chao MV, Calissano P, D’Adamio L (2011) APP is phosphorylated by TrkA and regulates NGF/TrkA signaling. J Neurosci 31:11756–11761
pubmed: 21849536
pmcid: 3319322
doi: 10.1523/JNEUROSCI.1960-11.2011
Matrone C, Luvisetto S, La Rosa LR, Tamayev R, Pignataro A, Canu N, Yang L, Barbagallo AP, Biundo F, Lombino F, Zheng H, Ammassari-Teule M, D’Adamio L (2012) Tyr682 in the Aβ-precursor protein intracellular domain regulates synaptic connectivity, cholinergic function, and cognitive performance. Aging Cell 6:1084–1093
doi: 10.1111/acel.12009
Molton SA, Todd DE, Cook SJ (2003) Selective activation of the c-Jun N-terminal kinase (JNK) pathway fails to elicit Bax activation or apoptosis unless the phosphoinositide 3′‐kinase (PI3K) pathway is inhibited. Oncogene 22:4690–4701
pubmed: 12879014
doi: 10.1038/sj.onc.1206692
Montalban E, Mattugini N, Ciarapica R, Provenzano C, Savino M, Scagnoli F, Prosperini G, Carissimi C, Fulci V, Matrone C, Calissano P, Nasi S (2014) MiR-21 is an NGF-modulated microRNA that supports NGF signaling and regulates neuronal degeneration in PC12 cells. Neuromolecular Med 16:415–430
pubmed: 24492999
pmcid: 4019824
doi: 10.1007/s12017-014-8292-z
Mufson EJ, Counts SE, Ginsberg SD, Mahady L, Perez SE, Massa SM, Longo FM, Ikonomovic MD (2019) Nerve growth factor pathobiology during the progression of Alzheimer’s disease. Front Neurosci 13:533
pubmed: 31312116
pmcid: 6613497
doi: 10.3389/fnins.2019.00533
Nielsen MS, Madsen P, Christensen EI, Nykjær A, Gliemann J, Kasper D, Pohlmann R, Petersen CM (2001) The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J 20:2180–2190
pubmed: 11331584
pmcid: 125444
doi: 10.1093/emboj/20.9.2180
Nielsen HM, Mulder SD, Belien JA, Musters RJ, Eikelenboom P, Veerhuis R (2010) Astrocytic A beta 1-42 uptake is determined by A beta-aggregation state and the presence of amyloid-associated proteins. Glia 58:1235–1246
pubmed: 20544859
doi: 10.1002/glia.21004
Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM (2004) Sortilin is essential for proNGF-induced neuronal cell death. Nature 427(6977):843–848
pubmed: 14985763
doi: 10.1038/nature02319
pmcid: 14985763
Oueslati AJ (2016) Implication of alpha-synuclein phosphorylation at S129 in synucleinopathies: what have we learned in the last decade? Parkinsons Dis 26(1):39–51
doi: 10.3233/JPD-160779
Pandey A, Singh P, Jauhari A, Singh T, Khan F, Pant AB, Parmar D, Yadav S (2015) Critical role of the miR-200 family in regulating differentiation and proliferation of neurons. J Neurochem 133:640–652
pubmed: 25753155
doi: 10.1111/jnc.13089
Parsi S, Smith PY, Goupil C, Dorval V, Hébert SS (2015) Preclinical evaluation of miR-15/107 family members as multifactorial drug targets for Alzheimer’s disease. Mol Ther Nucleic Acids 4(10):e256
Patel J, Fujisawa S, Berényi A, Royer S, Buzsáki G (2012) Traveling theta waves along the entire septotemporal axis of the hippocampus. Neuron 75:410–417
pubmed: 22884325
pmcid: 3427387
doi: 10.1016/j.neuron.2012.07.015
Patranabis S, Bhattacharyya SN (2016) Phosphorylation of Ago2 and subsequent inactivation of let-7a RNP-specific microRNAs control differentiation of mammalian sympathetic neurons. Mol Cell Biol 36:1260–1271
pubmed: 26858302
pmcid: 4836275
doi: 10.1128/MCB.00054-16
Pearson RCA, Gatter KC, Powell TPS (1983) The cortical relationships of certain basal ganglia and the cholinergic basal forebrain nuclei. Brain Res 261:327–330
pubmed: 6339004
doi: 10.1016/0006-8993(83)90638-8
Petersen PC, Buzsáki G (2020) Cooling of medial septum reveals theta phase lag coordination of hippocampal cell assemblies. Neuron 107:731–744.e3
Puzzo D, Lee L, Palmeri A, Calabrese G, Arancio O (2014) Behavioral assays with mouse models of Alzheimer’s disease: practical considerations and guidelines. Biochem Pharmacol 88:450–467
pubmed: 24462904
pmcid: 4014001
doi: 10.1016/j.bcp.2014.01.011
Roussarie JP, Yao V, Rodriguez-Rodriguez P, Oughtred R, Rust J, Plautz Z, Kasturia S, Albornoz C, Wang W, Schmidt EF, Dannenfelser R, Tadych A, Brichta L, Barnea-Cramer A, Heintz N, Hof PR, Heiman M, Dolinski K, Flajolet M, Troyanskaya OG, Greengard P (2020) Selective neuronal vulnerability in Alzheimer’s disease: a network-based analysis. Neuron 107:1–15
doi: 10.1016/j.neuron.2020.06.010
Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC (2006) Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51:29–42
Salta E, De Strooper B (2017) microRNA-132: a key noncoding RNA operating in the cellular phase of Alzheimer’s disease. FASEB J 31:424–433
pubmed: 28148775
doi: 10.1096/fj.201601308
Sassin I, Schultz C, Thal DR, Rüb U, Arai K, Braak E, Braak H (2000) Evolution of Alzheimer’s disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol 100:259–269
pubmed: 10965795
doi: 10.1007/s004019900178
Schettini G, Govoni S, Racchi M, Rodriguez G (2010) Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role—relevance for Alzheimer pathology. J Neurochem 115:1299–1308
pubmed: 21039524
doi: 10.1111/j.1471-4159.2010.07044.x
Schliebs R, Arendt T (2011) The cholinergic system in aging and neuronal degeneration. Behav Brain Res 221:555–563
Schmitz TW, Mur M, Aghourian M, Bedard M-A, Spreng RN, Alzheimer’s Disease Neuroimaging Initiative (2018) Longitudinal Alzheimer’s degeneration reflects the spatial topography of cholinergic basal forebrain projections. Cell Rep 24:38–46
pubmed: 29972789
doi: 10.1016/j.celrep.2018.06.001
Schubert M, Gautam D, Surjo D et al (2004) Role for neuronal insulin resistance in neurodegenerative diseases. Proc Natl Acad Sci U S A 101:3100–3105
pubmed: 14981233
pmcid: 365750
doi: 10.1073/pnas.0308724101
Selkoe DJ (2011) Resolving controversies on the path to Alzheimer’s therapeutics. Nat Med 17:1060–1065
pubmed: 21900936
doi: 10.1038/nm.2460
Selkoe DJ, Yamazaki T, Citron M, Podlisny MB, Koo EH, Teplow DB, Haass C (1996) The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann N Y Acad Sci 777:57–64
pubmed: 8624127
doi: 10.1111/j.1749-6632.1996.tb34401.x
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1:a006189
pubmed: 22229116
pmcid: 3234452
doi: 10.1101/cshperspect.a006189
Skeberdis VA, Lan J, Zheng X, Zukin RS, Bennett MVL (2001) Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci U S A 98:3561–3566
pubmed: 11248117
pmcid: 30692
doi: 10.1073/pnas.051634698
Sperling RA, Aisen PS, Beckett LA et al (2011) 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 7:280–292
pubmed: 21514248
pmcid: 3220946
doi: 10.1016/j.jalz.2011.03.003
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473
Spires-Jones TL, Hyman BT (2014) The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 82(4):756–771
pubmed: 24853936
pmcid: 4135182
doi: 10.1016/j.neuron.2014.05.004
Sposato V, Canu N, Fico E, Fusco S, Bolasco G, Ciotti MT, Spinelli M, Mercanti D, Grassi C, Triaca V, Calissano P (2019) The medial septum is insulin resistant in the AD presymptomatic phase: rescue by nerve growth factor-driven IRS1 activation. Mol Neurobiol 56:535–552
pubmed: 29736736
doi: 10.1007/s12035-018-1038-4
Stypulkowski PH, Stanslaski SR, Giftakis JE (2017) Modulation of hippocampal activity with fornix deep brain stimulation. Brain Stimul 10:1125–1132
Szutowicz A, Bielarczyk H, Jankowska-Kulawy A, Pawełczyk T, Ronowska A (2013) Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases. Neurochem Res 38:1523–1542
pubmed: 23677775
pmcid: 3691476
doi: 10.1007/s11064-013-1060-x
Takahashi M Kametani F, Nonaka T, Akiyama H, Hisanaga S, Hasegawa M (2015) Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau. Acta Neuropathol 129(6):895–907
Tarr PE, Contursi C, Roncarati R, Noviello C, Ghersi E, Scheinfeld MH, Zambrano N, Russo T, D’Adamio L (2002) Evidence for a role of the nerve growth factor receptor TrkA in tyrosine phosphorylation and processing of beta-APP. Biochem Biophys Res Commun 295(2):324–329
pubmed: 12150951
doi: 10.1016/S0006-291X(02)00678-2
Teipel SJ, Flatz WH, Heinsen H, Bokde AL, Schoenberg SO, Stockel S, Dietrich O, Reiser MF, Moller HJ, Hampel H (2005) Measurement of basal forebrain atrophy in Alzheimer’s disease using MRI. Brain 128(Part 11):2626–2644
pubmed: 16014654
doi: 10.1093/brain/awh589
Teipel SJ, Meindl T, Grinberg L, Grothe M, Cantero JL, Reiser MF, Möller H-J, Heinsen H, Hampel H (2011) The cholinergic system in mild cognitive impairment and Alzheimer’s disease: an in vivo MRI and DTI study. Hum Brain Mapp 32:1349–1362
pubmed: 20672311
doi: 10.1002/hbm.21111
Tenreiro S, Eckermann K, Outeiro TF (2014) Protein phosphorylation in neurodegeneration: friend or foe? Front Mol Neurosci 7:42
pubmed: 24860424
pmcid: 4026737
doi: 10.3389/fnmol.2014.00042
Terasawa K, Ichimura A, Sato F, Shimizu K, Tsujimoto G (2009) Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells. FEBS J. 276:3269–3276
pubmed: 19438724
doi: 10.1111/j.1742-4658.2009.07041.x
Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800
doi: 10.1212/WNL.58.12.1791
Tilvis RS, Kahonen-Vare MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE (2004) Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol Ser A Biol Sci Med Sci 59:M268–M274
doi: 10.1093/gerona/59.3.M268
Triaca V, Sposato V, Bolasco G, Ciotti MT, Pelicci P, Bruni AC, Cupidi C, Maletta R, Feligioni M, Nisticò R, Canu N, Calissano P (2016) NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer’s disease. Aging Cell 15:661–672
pubmed: 27076121
pmcid: 4933663
doi: 10.1111/acel.12473
Triaca V, Coccurello R, Giacovazzo G (2018) The neuronal Shc adaptor in Alzheimer’s disease. Aging 10(1):5–6
pubmed: 29362290
pmcid: 5811251
doi: 10.18632/aging.101368
Tsanov M (2017) Speed and oscillations: medial septum integration of attention and navigation. Front Syst Neurosci 11:67
Vaegter CB, Jansen P, Fjorback AW, Glerup S, Skeldal S, Kjolby M, Richner M, Erdmann B, Nyengaard JR, Tessarollo L, Lewin GR, Willnow TE, Chao MV, Nykjaer A (2011) Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling. Nat Neurosci 14:54–61
pubmed: 21102451
doi: 10.1038/nn.2689
Verma S, Kumar A, Tripathi T, Kumar A (2018) Muscarinic and nicotinic acetylcholine receptor agonists: current scenario in Alzheimer’s disease therapy. J Pharm Pharmacol 70(8):985–993
pubmed: 29663387
doi: 10.1111/jphp.12919
Vogels OJM, Broere CAJ, ter Laak HJ, ten Donkelaar HJ, Nieuwenhuys R, Schulte BPM (1990) Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease. Neurobiol Aging 11:3–13
pubmed: 2183081
doi: 10.1016/0197-4580(90)90056-6
Wang B, Yang L, Wang Z, Zheng H (2007) Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci U S A 104:14140–14145
pubmed: 17709753
pmcid: 1955810
doi: 10.1073/pnas.0704070104
Wang B, Pan L, Wei M, Wang Q, Liu WW, Wang N, Jiang XY, Zhang X, Bao L (2015) FMRP-mediated axonal delivery of miR-181d regulates axon elongation by locally targeting Map1b and Calm1. Cell Rep 13:2794–2807
pubmed: 26711345
doi: 10.1016/j.celrep.2015.11.057
pmcid: 26711345
Wang M, Qin L, Tang B (2019a) MicroRNAs in Alzheimer’s disease. Front Genet 10:153
pubmed: 30881384
pmcid: 6405631
doi: 10.3389/fgene.2019.00153
Wang W, Tanokashira D, Fukui Y, Maruyama M, Kuroiwa C, Saito T, Saido TC, Taguchi A (2019b) Serine phosphorylation of IRS1 correlates with Aβ-unrelated memory deficits and elevation in Aβ level prior to the onset of memory decline in AD. Nutrients 11:1942
pmcid: 6723493
doi: 10.3390/nu11081942
Whitehouse PJ, Price DL, Clark AW, Coyle JT, Delong MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126
pubmed: 7283399
doi: 10.1002/ana.410100203
pmcid: 7283399
Whitehouse PJ, PriceDL StrubleRG, Clark AW, Coyle JT, De-lon MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239
pubmed: 7058341
doi: 10.1126/science.7058341
Whitmer RA (2007) Type 2 diabetes and risk of cognitive impairment and dementia. Curr Neurol Neurosci Rep 7:373–380
pubmed: 17764626
doi: 10.1007/s11910-007-0058-7
pmcid: 17764626
Willette AA, Bendlin BB, Starks EJ et al (2015) Association of insulin resistance with cerebral glucose uptake in late middle–aged adults at risk for Alzheimer disease. JAMA Neurol 72:1013
pubmed: 26214150
pmcid: 4570876
doi: 10.1001/jamaneurol.2015.0613
Wu Q, Ye X, Xiong Y, Zhu H, Miao J, Zhang W, Wan J (2016) The protective role of microRNA-200c in Alzheimer’s disease pathologies is induced by beta amyloid-triggered endoplasmic reticulum stress. Front Mol Neurosci 9:140
pubmed: 28008308
pmcid: 5143617
Wurtman RJ (1992) Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci 15:117–122
pubmed: 1374967
doi: 10.1016/0166-2236(92)90351-8
pmcid: 1374967
Xu W, Weissmiller AM, White JA 2nd, Fang F, Wang X, Wu Y, Pearn ML, Zhao X, Sawa M, Chen S, Gunawardena S, Ding J, Mobley WC, Wu C (2016) Amyloid precursor protein-mediated endocytic pathway disruption induces axonal dysfunction and neurodegeneration. J Clin Invest 126(5):1815–1833
pubmed: 27064279
pmcid: 4855914
doi: 10.1172/JCI82409
Zatorre RJ, Fields RD, Johansen-Berg H (2012) Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 15(4):528–536
pubmed: 22426254
pmcid: 3660656
doi: 10.1038/nn.3045
Zhang YW, Thomposn R, Zang H, Xu H (2011) APP processing in Alzheimer’s disease. Mol Brain 4:3
pubmed: 21214928
pmcid: 3022812
doi: 10.1186/1756-6606-4-3
Zhang YW, Chen Y, Liu Y, Zhao Y, Liao FF, Xu H (2013) APP regulates NGF receptor trafficking and NGF-mediated neuronal differentiation and survival. PLoS One 8(11):e80571
pubmed: 24224055
pmcid: 3815101
doi: 10.1371/journal.pone.0080571
Zhao W-Q, Alkon DL (2001) Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol 177:125–134
pubmed: 11377828
doi: 10.1016/S0303-7207(01)00455-5
pmcid: 11377828
Zhu QB, Unmehopa U, Bossers K, Hu YT, Verwer R, Balesar R, Zhao J, Bao AM, Swaab D (2016) MicroRNA-132 and early growth response-1 in nucleus basalis of Meynert during the course of Alzheimer’s disease. Brain 139:908–921
pubmed: 26792551
doi: 10.1093/brain/awv383
pmcid: 26792551