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Transcriptional gender specific changes in the APP/PS1 mouse model of Alzheimer’s disease pathology

ABSTRACT: The prevalence of Alzheimer’s disease is significantly higher in women than in men, with recent estimates suggesting that two thirds of AD patients are females. However, the reason for this is unclear and complex, with the fact that women live longer than men being a likely contributor to the observed disparity. Given the complexity of AD and the restrictions in studying any gender-linked biological differences in patients, an established alternative is to study animal models of a disease. To determine if there are gender differences in the response of animals to amyloid deposit, a key pathological feature of AD, we did a genome-wide expression study on tissue obtained from the hippocampus and prefrontal cortex of male and female APP/PS1 mice at 8 months of age, a time at which significant cortical and hippocampal amyloid deposition is present. Amyloid deposit has previously been demonstrated in this model to be independent of gender. Regardless of the tissue sampled, we observed similar pathways affected in male and female mice. Focusing on major neurotransmitter and ionic pathways within the central nervous system reveal more profound gene expression changes in the prefrontal cortex and more restricted changes in the hippocampus. While the changes in the prefrontal cortex involved the same amount of genes in either gender only 60% of these are shown to overlap. In the hippocampus, distinctively fewer changes were observed in female mice than in male mice. By using pre-menopausal mice to investigation the gender differences in response to amyloid deposition, the effect of menopause and changes in progesterone and estrogen levels were eliminated in our study. While previous studies have focused on the genome-wide changes in AD models, the present study contributes to the existing literature on the gene changes in special relation to gender effect in AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE85162 | GEO | 2020/03/23

REPOSITORIES: GEO

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