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

Tamar Gefen*, Allegra Kawles, Beth Makowski-Woidan, Janessa Engelmeyer, Ivan Ayala, Payam Abbassian, Hui Zhang, Sandra Weintraub, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Emily Rogalski, M. Marsel Mesulam, Changiz Geula

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3177-3183
Number of pages7
JournalCerebral Cortex
Issue number7
StatePublished - Jul 1 2021


  • Alzheimer's disease
  • SuperAgers
  • entorhinal cortex
  • memory
  • stereology

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience


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