BIN1^K358R suppresses glial response to plaques in mouse model of Alzheimer's disease.

ABSTRACT:

Introduction

The BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.

Methods

To elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1^K358R knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology.

Results

The presence of the BIN1^K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Syna

SUBMITTER: Garcia-Agudo LF 

PROVIDER: S-EPMC11032570 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature