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

Abstract

INTRODUCTION: Preclinical studies reveal that the microbiome broadly affects immune responses and deposition and/or clearance of amyloid-beta (A{beta}) in mouse models of Alzheimers disease (AD). Whether the microbiome shapes central and peripheral immune profiles in AD models remains unknown. METHODS: We examined adaptive immune responses in two mouse models containing AD- related genetic predispositions (3xTg and 5xFAD) in the presence or absence of the microbiome. RESULTS: T and B cells were altered in brain-associated and systemic immune tissues between genetic models and wildtype mice, with earlier signs of immune activity in females. Systemic immune responses were modulated by the microbiome and differed by sex. Further, the absence of a microbiome in germ-free mice resulted in reduced cognitive deficits, primarily in females. DISCUSSION: These data reveal sexual dimorphism in early signs of immune activity and microbiome effects, and highlight an interesting interaction between sex and the microbiome in mouse models of AD.