Cathepsin B modulates microglial migration and phagocytosis of amyloid β in Alzheimer's disease through PI3K-Akt signaling.

ABSTRACT: The approval of anti-amyloid β (Aβ) monoclonal antibodies (lecanemab) for the treatment of patients with early preclinical stage of Alzheimer's disease (AD) by the Food and Drug Administration, suggests the reliability and importance of brain Aβ clearance for AD therapy. Microglia are the main phagocytes that clear Aβ in the brain, but the underlying regulatory mechanism is unclear. Here, we investigate the critical role of cathepsin B (CatB) in modulating microglial Aβ clearance from mouse brain. Wild-type or CatB^-/- mice were injected with Aβ into the hippocampus from 1 to 3 weeks. Mice were evaluated for cognitive change, Aβ metabolism, neuroinflammation. Microglia and neuron cultures were prepared to verify the in vivo results. The statistical analyses were performed by stud

SUBMITTER: Jiang M 

PROVIDER: S-EPMC11845476 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature