Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old

Brain. 2011 Dec;134(Pt 12):3708-15. doi: 10.1093/brain/awr308. Epub 2011 Nov 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Dementia / metabolism*
  • Dementia / pathology
  • Female
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Humans
  • Longitudinal Studies
  • Male
  • Neocortex / metabolism*
  • Neocortex / pathology
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • tau Proteins