Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer's rats.

TitleFemales exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer's rats.
Publication TypeJournal Article
Year of Publication2022
AuthorsChaudry O, Ndukwe K, Xie L, Figueiredo-Pereira M, Serrano P, Rockwell P
JournalSci Rep
Volume12
Issue1
Pagination19129
Date Published2022 Nov 09
ISSN2045-2322
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Mice, Transgenic, Neurodegenerative Diseases, Plaque, Amyloid, Presenilin-1, Rats, Rats, Inbred F344, Rats, Transgenic
Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is most prevalent in females. While estrogen provides neuroprotection in females, sex mediated differences in the development of AD pathology are not fully elucidated. Therefore, comparing events between sexes in early-stage AD pathology may reveal more effective therapeutic targets of intervention. To address sex differences, we analyzed early-stage 9-month male and female TgF344-AD (Tg-AD) rats, an AD model carrying the APPswe and Presenilin 1 (PS1ΔE9) mutations that develops progressive age-dependent AD pathology similar to humans. Tg-AD females significantly outperformed Tg-AD males in the active place avoidance (aPAT) test that assesses hippocampal-dependent spatial learning and memory. However, comparisons between Tg-AD male or female rats and their WT counterparts showed significant deficits for female but not male rats. Nevertheless, Tg-AD females experienced significantly less hippocampal neuronal loss with higher GluA2 subunit levels than Tg-AD males. Unexpectedly, Tg-AD females displayed higher levels of hippocampal amyloid plaques than Tg-AD males. Thus, we propose that GluA2 may provide a neuroprotective function for Tg-AD females in our rat model by mitigating cognitive impairment independently of amyloid plaques. Elucidating this protective mechanism in AD could lead to new targets for early intervention.

DOI10.1038/s41598-022-23801-w
Alternate JournalSci Rep
PubMed ID36352024
PubMed Central IDPMC9646806
Grant ListR01 AG057555 / AG / NIA NIH HHS / United States
R25 GM060665 / GM / NIGMS NIH HHS / United States