Neocortical and hippocampal amyloid-? 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-?, tau, TDP-43 and ?-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-?, tau, TDP-43 and ?-synuclein pathologies as well as hippocampal sclerosis. Amyloid-? and tau were the predominant pathologies in the 90+ Study cohort and both amyloid-? 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 ?-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-? 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-? pathology, dementia associated with an expansion in pathology, including increased neocortical tau and hippocampal amyloid-? plaques, more abundant neocortical amyloid-? deposition and hippocampal sclerosis with its attendant TDP-43 pathology.

SUBMITTER: Robinson JL 

PROVIDER: S-EPMC3235569 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature