Concomitant LATE-NC in Alzheimer's disease is not associated with increased tau or amyloid-β pathological burden.
Alzheimer's disease
LATE-NC
TDP-43
tau pathology
Journal
Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
14
06
2020
revised:
23
07
2020
accepted:
22
08
2020
pubmed:
9
9
2020
medline:
29
10
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is present in approximately 50% of Alzheimer's disease (AD) cases and is associated with accelerated cognitive decline. Studies indicate a potential synergistic relationship between LATE-NC and hyperphosphorylated tau. It is unknown if LATE-NC is an independent driver of cognitive impairment or exerts its influence through synergistic relationships with tau. This cliniconeuropathological study investigated the impact of LATE-NC on quantified measures of AD-associated pathology and its impact on clinical measures. A total of 61 AD cases underwent neuropathological assessment for LATE-NC and quantitative assessment [area covered by immunoreactivity (IR)] for early conformational tau (MC-1), late-stage hyperphosphorylated tau (AT8) and amyloid-β in the amygdala and five neocortical regions. Clinical measures included age of disease onset, final Mini-Mental State Examination (MMSE) score and rate of cognitive decline. LATE-NC was present in 41 AD cases (AD/LATE-NC; 67.2%). No significant differences in MC-1-IR, AT8-IR or 4G8-IR were observed in any region between AD/LATE-NC and AD without LATE-NC, indicating no accelerated aggregation or hyperphosphorylation of tau proteins in the AD/LATE-NC cases. Final MMSE was significantly lower in AD/LATE-NC cases and was significantly associated with LATE-NC score even when controlled for the presence of both MC-1-IR and AT8-IR (P = 0.009). The presence of LATE-NC in AD is not associated with an increase in the burden of early or late tau or Aβ pathology. LATE-NC is associated with a lower final MMSE score independent of tau pathology.
Substances chimiques
Amyloid beta-Peptides
0
DNA-Binding Proteins
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-734Subventions
Organisme : Medical Research Council
ID : G0502157
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400074
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900652
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
Références
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 2012; 8(1): 1-13
Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012; 123(1): 1-11
Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol 2009; 118(1): 5-36
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, et al. TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Ann Neurol 2007; 61(5): 435-45
Josephs KA, Murray ME, Whitwell JL, Parisi JE, Petrucelli L, Jack CR, et al. Staging TDP-43 pathology in Alzheimer's disease. Acta Neuropathol 2014; 127(3): 441-50
Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M, et al. Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 2008; 70(19 Pt 2): 1850-7
Arai T, Mackenzie IR, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, et al. Phosphorylated TDP-43 in Alzheimer's disease and dementia with Lewy bodies. Acta Neuropathol 2009; 117(2): 125-36
Davidson YS, Raby S, Foulds PG, Robinson A, Thompson JC, Sikkink S, et al. TDP-43 pathological changes in early onset familial and sporadic Alzheimer's disease, late onset Alzheimer's disease and Down's syndrome: association with age, hippocampal sclerosis and clinical phenotype. Acta Neuropathol 2011; 122(6): 703-13
Josephs KA, Whitwell JL, Tosakulwong N, Weigand SD, Murray ME, Liesinger AM, et al. TAR DNA-binding protein 43 and pathological subtype of Alzheimer's disease impact clinical features. Ann Neurol 2015; 78(5): 697-709
Josephs KA, Whitwell JL, Weigand SD, Murray ME, Tosakulwong N, Liesinger AM, et al. TDP-43 is a key player in the clinical features associated with Alzheimer's disease. Acta Neuropathol 2014; 127(6): 811-24
Wilson RS, Yu L, Trojanowski JQ, Chen EY, Boyle PA, Bennett DA, et al. TDP-43 pathology, cognitive decline, and dementia in old age. JAMA neurology. 2013; 70(11): 1418-24
Uchino A, Takao M, Hatsuta H, Sumikura H, Nakano Y, Nogami A, et al. Incidence and extent of TDP-43 accumulation in aging human brain. Acta neuropathologica communications. 2015; 3: 35
McAleese KE, Walker L, Erskine D, Thomas AJ, McKeith IG, Attems J. TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing. Brain Pathol. 2016; 27(4): 472-9
Bigio EH. TDP-43 variants of frontotemporal lobar degeneration. J Mol Neurosci. 2011; 45(3): 390-401
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314(5796): 130-3
Josephs KA, Stroh A, Dugger B, Dickson DW. Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes. Acta Neuropathol 2009; 118(3): 349-58
Josephs KA, Murray ME, Whitwell JL, Tosakulwong N, Weigand SD, Petrucelli L, et al. Updated TDP-43 in Alzheimer's disease staging scheme. Acta Neuropathol 2016; 131(4): 571-85
Nelson PT, Dickson DW, Trojanowski JQ, Jack CR, Boyle PA, Arfanakis K, et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 2019; 142(6): 1503-27
Josephs KA, Dickson DW, Tosakulwong N, Weigand SD, Murray ME, Petrucelli L, et al. Rates of hippocampal atrophy and presence of post-mortem TDP-43 in patients with Alzheimer's disease: a longitudinal retrospective study. Lancet Neurol 2017; 16(11): 917-924
Davis SA, Gan KA, Dowell JA, Cairns NJ, Gitcho MA. TDP-43 expression influences amyloidbeta plaque deposition and tau aggregation. Neurobiol Dis. 2017; 103: 154-62
Gu J, Wu F, Xu W, Shi J, Hu W, Jin N, et al. TDP-43 suppresses tau expression via promoting its mRNA instability. Nucleic Acids Res 2017; 45(10): 6177-93
Spires-Jones TL, Attems J, Thal DR. Interactions of pathological proteins in neurodegenerative diseases. Acta Neuropathol 2017; 134(2): 187-205
Nakashima-Yasuda H, Uryu K, Robinson J, Xie SX, Hurtig H, Duda JE, et al. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 2007; 114(3): 221-9
Smith VD, Bachstetter AD, Ighodaro E, Roberts K, Abner EL, Fardo DW, et al. Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi. Brain Pathol. 2018; 28(2): 264-73
Josephs KA, Murray ME, Tosakulwong N, Weigand SD, Serie AM, Perkerson RB, et al. Pathological, imaging and genetic characteristics support the existence of distinct TDP-43 types in non-FTLD brains. Acta Neuropathol 2019; 137(2): 227-38
Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003; 60(9): 1495-500
Dawe RJ, Bennett DA, Schneider JA, Arfanakis K. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. PLoS One 2011; 6(10): e26286
Buciuc M, Wennberg AM, Weigand SD, Murray ME, Senjem ML, Spychalla AJ, et al. Effect modifiers of TDP-43-associated hippocampal atrophy rates in patients with Alzheimer's disease neuropathological changes. J Alzheimers Dis 2020; 73(4): 1511-23
Thal DR, Rub U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 2002; 58(12): 1791-800
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 2006; 112(4): 389-404
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991; 41(4): 479-86
McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65(12): 1863-72
Skrobot OA, Attems J, Esiri M, Hortobagyi T, Ironside JW, Kalaria RN, et al. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. Brain 2016; 139(11): 2957-69
Walker L, McAleese KE, Johnson M, Khundakar AA, Erskine D, Thomas AJ, et al. Quantitative neuropathology: an update on automated methodologies and implications for large scale cohorts. J Neural Transm 2017; 124(6): 671-83
Jicha GA, Bowser R, Kazam IG, Davies P. Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau. J Neurosci Res 1997; 48(2): 128-32
Uboga NV, Price JL. Formation of diffuse and fibrillar tangles in aging and early Alzheimer's disease. Neurobiol Aging 2000; 21(1): 1-10
Augustinack JC, Schneider A, Mandelkow EM, Hyman BT. Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta Neuropathol 2002; 103(1): 26-35
McAleese KE, Firbank M, Dey M, Colloby SJ, Walker L, Johnson M, et al. Cortical tau load is associated with white matter hyperintensities. Acta Neuropathol Commun. 2015; 3: 60
McAleese KE, Walker L, Graham S, Moya ELJ, Erskine D, Johnson M, et al. White matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology but not with small vessel disease. Acta Neuropathol 2017; 134(3): 459-473
Yamamoto Y, Ihara M, Tham C, Low RW, Slade JY, Moss T, et al. Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL. Stroke 2009; 40(6): 2004-11
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98
Olichney JM, Galasko D, Salmon DP, Hofstetter CR, Hansen LA, Katzman R, et al. Cognitive decline is faster in Lewy body variant than in Alzheimer's disease. Neurology 1998; 51(2): 351-7
Dickson DW, Davies P, Bevona C, Van Hoeven KH, Factor SM, Grober E, et al. Hippocampal sclerosis: a common pathological feature of dementia in very old (> or = 80 years of age) humans. Acta Neuropathol 1994; 88(3): 212-21
Hokkanen SRK, Hunter S, Polvikoski TM, Keage HAD, Minett T, Matthews FE, et al. Hippocampal sclerosis, hippocampal neuron loss patterns and TDP-43 in the aged population. Brain Pathol. 2018; 28(4): 548-59
Kero M, Raunio A, Polvikoski T, Tienari PJ, Paetau A, Myllykangas L. Hippocampal sclerosis in the oldest old: a Finnish population-based study. J Alzheimer's Dis 2018; 63(1): 263-72
Gu J, Chen F, Iqbal K, Gong CX, Wang X, Liu F. Transactive response DNA-binding protein 43 (TDP-43) regulates alternative splicing of tau exon 10: implications for the pathogenesis of tauopathies. J Biol Chem 2017; 292(25): 10600-12
Latimer CS, Burke BT, Liachko NF, Currey HN, Kilgore MD, Gibbons LE, et al. Resistance and resilience to Alzheimer's disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort. Acta Neuropathol Commun. 2019; 7(1): 91
Jeganathan S, Hascher A, Chinnathambi S, Biernat J, Mandelkow EM, Mandelkow E. Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of Tau and generates a pathological (MC-1) conformation. J Biol Chem. 2008; 283(46): 32066-76
Niblock M, Hortobagyi T, Troakes C, Al-Sarraj S, Spickett C, Jones R, et al. Lack of association between TDP-43 pathology and tau mis-splicing in Alzheimer's disease. Neurobiol Aging 2016; 37: 45-6
Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol 2016; 79(1): 110-9
Hanna Al-Shaikh FS, Duara R, Crook JE, Lesser ER, Schaeverbeke J, Hinkle KM, et al. Selective vulnerability of the nucleus basalis of meynert among neuropathologic subtypes of Alzheimer disease. JAMA Neurol. 2020; 77(2): 225
Gordon BA, Blazey TM, Christensen J, Dincer A, Flores S, Keefe S, et al. Tau PET in autosomal dominant Alzheimer's disease: relationship with cognition, dementia and other biomarkers. Brain 2019; 142(4): 1063-76
Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, et al. Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol. 2010; 20(1): 66-79
Robinson AC, Thompson JC, Weedon L, Rollinson S, Pickering-Brown S, Snowden JS, et al. No interaction between tau and TDP-43 pathologies in either frontotemporal lobar degeneration or motor neurone disease. Neuropathol Appl Neurobiol 2014; 40(7): 844-54
Chornenkyy Y, Fardo DW, Nelson PT. Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy. Lab Invest 2019; 99(7): 993-1007