Neocortical and hippocampal amyloid-β and tau measures associate with dementia in the oldest-old
Open accessAbstract
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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Even in extreme old age, the presence of many neocortical NFTs correlates with antemortem cognitive decline.
“Even in extreme old age, the presence of many neocortical NFTs correlates with antemortem cognitive decline (105, 188-191).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [191]
Numerous studies have documented a strong link between neocortical NFTs and cognitive loss.
“On the other hand, numerous studies have documented a strong link between neocortical NFTs and cognitive loss[26, 46, 48, 97, 123, 160, 169].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [123]
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- Authors
- Robinson, J. L., Geser, F., Corrada, M. M., Berlau, D. J., Arnold, S. E., Lee, V. M.-Y., Kawas, C. H., & Trojanowski, J. Q.
- Affiliations
- University of Pennsylvania (US)
- University of California, Irvine (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-11-25
- Volume
- 134
- Issue
- 12
- Pages
- 3708-3715
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC3235569
- OpenAlex
- W2126165228
- Cited by
- 88
- References
- 35
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 3 · 2021: 8 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 15 · 2012: 10
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Alzheimer's Association
- University of Pennsylvania
- National Institutes of Health (AG 10 124, 5p50mh064045-10, AG 17586, AG16573, MH64045)
- University of California, Irvine
- National Institute on Aging (AG21055, R01AG021055, AG 16573, P30AG010124, P50AG016573, P01AG017586, AG17586, AG-10124, U19AG010483)
- National Institute of Mental Health (P50 MH-064045, MH64045)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, dementia, oldest old, amyloid-beta, tau protein, TDP-43, alpha-synuclein, hippocampal sclerosis, Braak staging
- MeSH terms
- Aged, 80 and over, Dementia, Female, Hippocampus, Humans, Longitudinal Studies, Male, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Neocortex, Plaque, Amyloid
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