p16+p21-expressing senescent cells accumulate in the aging brain — particularly in astrocytes, microglia, and neurons bearing neurofibrillary tangles. Their SASP (IL-6, CXCL1, CXCL10) drives neuroinflammation, impairs hippocampal neurogenesis, and amplifies tau and amyloid pathology. Clearance of brain senescent cells in tau-transgenic mice significantly reduces tau spreading and improves cognitive performance.

Should people with APOE4 genotype prioritize brain senolytics?

APOE4 carriers have elevated Alzheimer's risk driven partly by impaired microglial senescent cell clearance. Fisetin-based senolytic protocols are a particularly rational preventive strategy for APOE4 carriers, ideally started in their 40s.

Can senolytics replace Alzheimer's medications?

No. Established Alzheimer's disease requires the standard of care. Senolytics may complement treatment and offer prevention value; they are not currently treatments for established disease.