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Cited by 305Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

Hippocampal sclerosis and TDP ‐43 pathology in aging and A lzheimer disease

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Nag, Sukriti, Yu, Lei, Capuano, Ana W., Wilson, Robert S., Leurgans, Sue E., Bennett, David A., Schneider, Julie A.·2015·Annals of Neurology
DOI 10.1002/ana.24388PMC PMC4447563
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Abstract

OBJECTIVE: To investigate the association of hippocampal sclerosis (HS) with TAR-DNA binding protein of 43kDa (TDP-43) and other common age-related pathologies, dementia, probable Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive domains in community-dwelling older subjects. METHODS: Diagnoses of dementia, probable AD, and MCI in 636 autopsied subjects from the Religious Order Study and the Rush Memory and Aging Project were based on clinical evaluation and cognitive performance tests. HS was defined as severe neuronal loss and gliosis in the hippocampal CA1 and/or subiculum. The severity and distribution of TDP-43 were assessed, and other age-related pathologies were also documented. RESULTS: HS was more common in those aged >90 years (18.0%) compared to younger subjects (9.2%). HS cases commonly coexisted with TDP-43 pathology (86%), which was more severe (p < 0.001) in HS cases. Although HS also commonly coexisted with AD and Lewy body pathology; only TDP-43 pathology increased the odds of HS (odds ratio [OR] = 2.63, 95% confidence interval [CI] = 2.07-3.34). In logistic regression models accounting for age, TDP-43, and other common age-related pathologies, HS cases had higher odds of dementia (OR = 3.71, 95% CI = 1.93-7.16), MCI, and probable AD (OR = 3.75, 95% CI = 2.01-7.02). In linear regression models, including an interaction term for HS and TDP-43 pathology, HS with coexisting TDP-43 was associated with lower function in multiple cognitive domains, whereas HS without TDP-43 did not have statistically significant associations. TDP-43 without HS was separately related to lower episodic memory. INTERPRETATION: The combined roles of HS and TDP-43 pathology are significant factors underlying global cognitive impairment and probable AD in older subjects.

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  • The 4-stage classification of TDP-43 distribution was based on previous studies.

    “In this study, we used a 4-stages classification of TDP-43 distribution based on previous studies [30,42]”

    From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [42]

    The Methods (Immunohistochemical studies) explicitly recognize three stages of TDP-43 distribution, not four. The paper says its assessment was described previously, but it does not support the attributed four-stage classification. (LLM, conf=0.90)

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Research works printed but not linked: 30

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Cited by

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Authors
Nag, S., Yu, L., Capuano, A. W., Wilson, R. S., Leurgans, S. E., Bennett, D. A., & Schneider, J. A.
Affiliations
Rush University Medical Center (US)
Corresponding author
Nag, Sukriti
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2015-04-22
Volume
77
Issue
6
Pages
942-952
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.24388
PMC
PMC4447563
OpenAlex
W1931319403
Cited by
305
References
5
Citations by year
2026: 16 · 2025: 31 · 2024: 24 · 2023: 27 · 2022: 33 · 2021: 31 · 2020: 32 · 2019: 33 · 2018: 30 · 2017: 19 · 2016: 18 · 2015: 10 · 2014: 1
FWCI
20.85
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG17917, P30AG10161, R01AG15819, R01AG42210)
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
hippocampal sclerosis, TDP-43 pathology, Alzheimer's disease, mild cognitive impairment, dementia, Lewy body pathology, aging, cognitive impairment, episodic memory, neuronal loss, gliosis, older adults, Rush Memory and Aging Project
MeSH terms
Aged, Aged, 80 and over, Aging, Alzheimer Disease, DNA-Binding Proteins, Female, Hippocampus, Humans, Male, Sclerosis, Cognitive Dysfunction

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