Faculty Collaboration Database

The detrimental effects of APOE4 on risk for Alzheimer's disease may result from altered dendritic spine density, synaptic proteins, and estrogen receptor alpha. Neurobiol Aging 2022 Apr;112:74-86

Date

01/21/2022

Pubmed ID

35051676

Pubmed Central ID

PMC8976726

DOI

10.1016/j.neurobiolaging.2021.12.006

Scopus ID

2-s2.0-85122971375 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

Women carriers of APOE4, the greatest genetic risk factor for late-onset Alzheimer's disease (AD), are at highest risk of developing AD, yet factors underlying interactions between APOE4 and sex are not well characterized. Here, we examined how sex and APOE3 or APOE4 genotypes modulate object and spatial memory, dendritic spine density and branching, and protein expression in 6-month-old male and female E3FAD and E4FAD mice (APOE^+/+/5xFAD^+/-). APOE4 negatively impacted object recognition and spatial memory, with male E3FADs exhibiting the best memory across 2 object-based tasks. In both sexes, APOE4 reduced basal dendritic spine density in the medial prefrontal cortex and dorsal hippocampus. APOE4 reduced dorsal hippocampal levels of PDS-95, synaptophysin, and phospho-CREB, yet increased levels of ERα. E4FAD females exhibited strikingly increased GFAP levels, in addition to the lowest levels of PSD-95 and pCREB. Overall, our results suggest that APOE4 negatively impacts object memory, dendritic spine density, and levels of hippocampal synaptic proteins and ERα. However, the general lack of sex differences or sex by genotype interactions suggests that the sex-specific effects of APOE4 on AD risk may be related to factors unexplored in the present study.

Author List

Taxier LR, Philippi SM, York JM, LaDu MJ, Frick KM

Author

Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Alzheimer Disease
Animals
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E
Dendritic Spines
Estrogen Receptor alpha
Female
Humans
Male
Mice
Mice, Transgenic