An unexpected molecular explanation for how tau aggregation begins in Alzheimer’s disease

Nature Neuroscience, Published online: 29 May 2026; doi:10.1038/s41593-026-02298-w Disruption of a neuronal-specific protein degradation system, the plasma membrane-bound neuroproteasome, triggers the conversion of endogenous tau into aggregates that mirror those seen in patients with Alzheimer’s disease (AD). Aging and APOE4 — the largest risk factors for AD — induce neuroproteasome loss, which provides a potential mechanistic basis for sporadic AD.