For instance, amyloid-centric models reproduce plaque formation but often lack tau pathology, vascular dysfunction and metabolic decline → partially explaining limited efficacy of late-stage anti-Aβ therapies [215,216], while models incorporating inflammation, tau, lipid metabolism or mitochondrial impairment align more closely with integrated biomarkers observed in clinical AD cohorts [217,218]. Here, MAPT is linked to Alzheimer disease.