Document Detail

Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old.
MedLine Citation:
PMID:  22120149     Owner:  NLM     Status:  MEDLINE    
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.
John L Robinson; Felix Geser; Maria M Corrada; Daniel J Berlau; Steven E Arnold; Virginia M-Y Lee; Claudia H Kawas; John Q Trojanowski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-26
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  134     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  2012-02-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  3708-15     Citation Subset:  AIM; IM    
Center for Neurodegenerative Disease Research, Institute on Ageing, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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MeSH Terms
Aged, 80 and over
Amyloid beta-Peptides / metabolism*
Dementia / metabolism*,  pathology
Hippocampus / metabolism*,  pathology
Longitudinal Studies
Neocortex / metabolism*,  pathology
Neurofibrillary Tangles / metabolism,  pathology
Plaque, Amyloid / metabolism,  pathology
tau Proteins / metabolism*
Grant Support
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/tau Proteins

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