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APOE genotype and sex influence memory and dendritic spine density in an EFAD mouse model of Alzheimer’s disease
Author(s) -
Taxier Lisa R,
Philippi Sarah M,
York Jason,
LaDu Mary Jo,
Frick Karyn M
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047563
Subject(s) - dendritic spine , apolipoprotein e , genotype , hippocampus , prefrontal cortex , memory impairment , basal (medicine) , biology , neuroscience , hippocampal formation , psychology , endocrinology , medicine , disease , genetics , gene , cognition , insulin
Background Women carriers of the APOE4 genotype, which is the leading genetic risk factor for late‐onset Alzheimer’s disease (AD), are more likely than women carriers of other APOE genotypes and men of any APOE genotype to develop AD. However, factors underlying the interaction between APOE genotype and sex are not well characterized. The goal of this study was to examine the effects of sex and APOE genotype on memory function and dendritic spine density in a mouse model of AD. Methods Six month‐old gonadally‐intact male and female transgenic (Tg) mice expressing 5 familial AD mutations (5xFAD +/‐ ) and human APOE3 +/+ (E3FAD) or APOE4 +/+ (E4FAD) were trained on object recognition (OR) and object placement (OP) tasks designed to test object recognition and spatial memory formation. Memory for previously seen objects or locations was tested 24 or 4 hours later, respectively. Two weeks after the conclusion of behavioral testing, mice were retrained with novel objects, and brains were collected for Golgi staining. Following staining, apical and basal dendritic spines in the dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) were counted and classified by morphological type. Results Male E3FAD mice exhibited intact memory for previously seen objects or locations, whereas male E4FADs and female E3FAD or E4FAD mice did not. The density of total, mushroom, and stubby spines on basal CA1 and mPFC dendrites was lower for E4FAD mice of both sexes compared to E3FAD mice. Preliminary data suggest a similar pattern for mPFC apical spine density. Conclusions These data suggest that APOE genotype and sex influence object recognition and spatial memory formation, and that APOE4 genotype is associated with reduced density of mature and immature spines in CA1 and the mPFC.