Microglial MS4A4A Protects against Epileptic Seizures in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is a predominant neurodegenerative disorder worldwide, with epileptic seizures being a common comorbidity that can exacerbate cognitive deterioration in affected individuals, thus highlighting the importance of early therapeutic intervention. It is determined that deletion of Ms4a4a, an AD-associated gene, exacerbates seizures in amyloid β (Aβ)-driven AD mouse model. MS4A4A is significantly upregulated in brain lesions in patients with epilepsy. Single-cell sequencing reveals that MS4A4A is highly expressed in microglia within these lesions, linked to enhanced phagocytic activity. Mechanistic investigation delineates that deletion of Ms4a4a impairs microglial phagocytosis, accompanied by diminished calcium influx and disruptions in mitochondrial metabolic fitness.

SUBMITTER: Jiang M 

PROVIDER: S-EPMC12165070 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature