Endosomal pathway dysfunction is the earliest known cytopathology of Alzheimer's disease (AD), with endosomal anomalies emerging years, possibly decades, before β-amyloid and tau tangles (Cataldo et al., 2000; Colacurcio et al., 2018; Pensalfini et al., 2020; Fahimi et al., 2021). Here, MAPT is linked to Alzheimer disease.