| Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old. | |
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MedLine Citation:
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PMID: 22120149 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-11-26 |
Journal Detail:
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Title: Brain : a journal of neurology Volume: 134 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-15 Completed Date: 2012-02-09 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
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Languages: eng Pagination: 3708-15 Citation Subset: AIM; IM |
Affiliation:
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Center for Neurodegenerative Disease Research, Institute on Ageing, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged, 80 and over Amyloid beta-Peptides / metabolism* Dementia / metabolism*, pathology Female Hippocampus / metabolism*, pathology Humans Longitudinal Studies Male Neocortex / metabolism*, pathology Neurofibrillary Tangles / metabolism, pathology Plaque, Amyloid / metabolism, pathology tau Proteins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AG10124/AG/NIA NIH HHS; AG16573/AG/NIA NIH HHS; AG17586/AG/NIA NIH HHS; AG21055/AG/NIA NIH HHS; MH64045/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/tau Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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