NOTCH3 Mutation Causes Glymphatic Impairment and Promotes Brain Senescence in CADASIL.

ABSTRACT:

Aims

The aim of this study is to investigate the role of glymphatic function of cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), the most common monogenic small vessel disease caused by NOTCH3 mutation, and to explore potential therapeutic strategies to improve glymphatic function.

Methods

We assessed glymphatic influx and efflux function in CADASIL mouse models (Notch3^R170C) and correlated these findings with brain atrophy in CADASIL patients. We also investigated the underlying mechanisms of glymphatic impairment, focusing the expression of AQP4 in astrocytic endfeet.

Results

CADASIL mouse exhibited both impaired glymphatic influx and efflux, which impedes waste clearance and promotes brain senescence. In

SUBMITTER: Li C 

PROVIDER: S-EPMC11760990 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature