Although biomarker development, in particular focusing on amyloid-β (Aβ) and paired helical filament tau, is improving the diagnostic efficacy of Alzheimer’s disease (AD), the invasive procedure of cerebrospinal fluid (CSF) testing and the limited availability of positron emission tomography (PET) impede their wide clinical application. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.