Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner

Nature Neuroscience, Published online: 29 May 2026; doi:10.1038/s41593-026-02297-x

A cellular explanation for how tau aggregates into fibrils in Alzheimer’s disease has been elusive. This paper identifies the failure of ‘neuroproteasomes’ as sufficient to convert tau into paired helical filaments, a process regulated by ApoE and aging.