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Paucity of Entorhinal Cortex Pathology of the Alzheimer's Type in SuperAgers with Superior Memory Performance.

Authors
  • Gefen, Tamar1, 2
  • Kawles, Allegra1
  • Makowski-Woidan, Beth1
  • Engelmeyer, Janessa1
  • Ayala, Ivan1
  • Abbassian, Payam1
  • Zhang, Hui1, 3
  • Weintraub, Sandra1, 2
  • Flanagan, Margaret E1, 4
  • Mao, Qinwen1, 4
  • Bigio, Eileen H1, 4
  • Rogalski, Emily1, 2
  • Mesulam, M Marsel1, 5
  • Geula, Changiz1, 6
  • 1 Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 2 Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 3 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 4 Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 5 Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 6 Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Type
Published Article
Journal
Cerebral Cortex
Publisher
Oxford University Press
Publication Date
Jun 10, 2021
Volume
31
Issue
7
Pages
3177–3183
Identifiers
DOI: 10.1093/cercor/bhaa409
PMID: 33592091
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Advancing age is typically associated with declining memory capacity and increased risk of Alzheimer's disease (AD). Markers of AD such as amyloid plaques (AP) and neurofibrillary tangles (NFTs) are commonly found in the brains of cognitively average elderly but in more limited distribution than in those at the mild cognitive impairment and dementia stages of AD. Cognitive SuperAgers are individuals over age 80 who show superior memory capacity, at a level consistent with individuals 20-30 years their junior. Using a stereological approach, the current study quantitated the presence of AD markers in the memory-associated entorhinal cortex (ERC) of seven SuperAgers compared with six age-matched cognitively average normal control individuals. Amyloid plaques and NFTs were visualized using Thioflavin-S histofluorescence, 6E10, and PHF-1 immunohistochemistry. Unbiased stereological analysis revealed significantly more NFTs in ERC in cognitively average normal controls compared with SuperAgers (P < 0.05) by a difference of ~3-fold. There were no significant differences in plaque density. To highlight relative magnitude, cases with typical amnestic dementia of AD showed nearly 100 times more entorhinal NFTs than SuperAgers. The results suggest that resistance to age-related neurofibrillary degeneration in the ERC may be one factor contributing to preserved memory in SuperAgers. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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