Microglial Deletion of Hrh4 Alleviates Alzheimer's Disease Pathologies by Enhancing Microglial Phagocytosis of Amyloid-β and Tau.

ABSTRACT: Amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) aggregation are hallmark pathogenic events in Alzheimer's disease (AD). Microglial clearance of these toxic aggregates is essential, yet the underlying mechanisms remain poorly understood. This study demonstrates that low-dose ionizing radiation (LDIR) provides protection against Aβ toxicity in vitro and rescues cognitive deficits in sporadic, young, and aged familial AD mouse models, including reductions in Aβ plaque, tauopathy, and microgliosis, while promoting microglial phagocytosis in aged 3xTg-AD mice. Transcriptomic analysis identifies VUF6002, a histamine H4 receptor (H₄R) antagonist, which mimics the beneficial effects of LDIR by promoting microglial activity. VUF6002 treatment restores cognitive function in aged 3xT

SUBMITTER: Xu YJ 

PROVIDER: S-EPMC12786338 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature