The microbiome impacts immunity in mouse models of Alzheimer's disease in a sex-specific manner.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B117
Abstract ID: 5811

Presenting Author:
John W Bostick , Postdoctoral Scholar at Caltech

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles, leading to neuronal death and decline in cognitive function. Rodent models of AD are important tools to study disease mechanisms and test potential interventions. Studies in mice have shown that the microbiome broadly affects immune responses, microglial activation states, and the deposition and/or clearance of Aβ. Few studies have evaluated central and peripheral immunity in AD models with respect to the microbiome. We examined immune responses in two mouse models of AD (3xTg and 5xFAD) in the presence or absence of the microbiome utilizing specific pathogen free (SPF) and germ-free (GF) mice. We found elevated adaptive immunity at the earliest ages examined. In 3xTg mice, local T and B cell numbers were elevated in female mice regardless of microbiome status, but not male mice. Systemic immune responses were modulated by the microbiome and differed by sex with enhanced T and B cell numbers in males. These data reveal sexual dimorphism in both inflammation onset and the effects of the microbiome in 3xTg mice. Unexpectedly, early inflammatory responses were restricted to the spleen and intestines in 5xFAD mice and were characterized by increased interleukin (IL)-17A-producing CD4+ T cells. Together, these data reveal interactions between sex and the microbiome that impact immunity in transgenic mouse models of AD.