Reduction in GABAB on glia induce Alzheimer?s disease related changes

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques (A beta), neuro-fibrillary tangles (NFT), and neuroinflammation. Data have demonstrated that neuroinflammation contributes to A beta and NFT onset and progression, indicating inflammation and glial signaling is vital to understanding AD. A previous investigation demonstrated a significant decrease of the GABAB receptor (GABABR) in APP/PS1 mice (Salazar et al., 2021). To determine if changes in GABABR restricted to glia serve a role in AD, we developed a mouse model with a reduction of GABABR restricted to macrophages, GAB/CX3ert. This model exhibits changes in gene expression and electrophysiological alterations similar to amyloid mouse models of AD. Crossing the GAB/CX3ert mouse with APP/PS1 resulted in significant increases in A beta pathology. Our data demonstrates that decreased GABABR on macrophages leads to several changes observed in AD mouse models, as well as exacer-bation of AD pathology when crossed with existing models. These data suggest a novel mechanism in AD pathogenesis.

Automated summary

Alzheimer's Disease (AD) is characterized by beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroinflammation plays a crucial role in the onset and progression of AD. Previous studies have shown a decrease in GABAB receptor (GABABR) in AD mouse models. By developing a mouse model with reduced GABABR restricted to macrophages, significant increases in beta-amyloid pathology were observed when crossed with existing AD models. This suggests a novel mechanism in the pathogenesis of AD.