title: Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old.
abstract: The emergence of longevity in the modern world has brought a sense of urgency to understanding age-related neurodegenerative diseases such as Alzheimer's disease. Unfortunately, there is a lack of consensus regarding the correlation between the pathological substrates of neurodegeneration and dementia status, particularly in the oldest-old. To better understand the pathological correlates of dementia in the oldest-old, we characterized the topographical spread and severity of amyloid-β, tau, TDP-43 and α-synuclein pathologies in the 90+ Study, a prospective longitudinal population-based study of ageing and dementia. Neuropathological analysis with immunohistochemically labelled sections was carried out blind to clinical diagnosis on the first 108 participants of the 90+ Study who came to autopsy including participants with dementia (n = 66) and without dementia (n = 42). We used quantitative and/or semi-quantitative measures to assess the burden of amyloid-β, tau, TDP-43 and α-synuclein pathologies as well as hippocampal sclerosis. Amyloid-β and tau were the predominant pathologies in the 90+ Study cohort and both amyloid-β area and tau area occupied measures were strongly associated with the presence of dementia, as was Braak staging but semi-quantitative plaque scores were not. Notably, TDP-43 pathology also correlated with dementia, while α-synuclein distribution did not. In addition, hippocampal sclerosis was specific to participants with dementia and correlated with the presence of limbic TDP-43. In contrast to previous reports, we found that tau and amyloid-β continue to be robust pathological correlates of dementia, even in the oldest-old. While individuals with no dementia had limited hippocampal tau and neocortical amyloid-β pathology, dementia associated with an expansion in pathology, including increased neocortical tau and hippocampal amyloid-β plaques, more abundant neocortical amyloid-β deposition and hippocampal sclerosis with its attendant TDP-43 pathology.
authors: Center for Neurodegenerative Disease Research, Institute on Ageing, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: John L
authors: JL
authors: Robinson
authors: Felix
authors: F
authors: Geser
authors: Maria M
authors: MM
authors: Corrada
authors: Daniel J
authors: DJ
authors: Berlau
authors: Steven E
authors: SE
authors: Arnold
authors: Virginia M-Y
authors: VM
authors: Lee
authors: Claudia H
authors: CH
authors: Kawas
authors: John Q
authors: JQ
authors: Trojanowski
mesh_terms: D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins