In a recent longitudinal study of tau PET in the ADNI cohort, higher polygenic risk for Alzheimer’s disease was associated with accelerated increase in tau signal in the brain, and this effect was modulated by amyloid pathology: A+ participants showed a stronger effect of PRS on tau accumulation.65 Our longitudinal analysis, which combined CSF and PET data to maximize the sample size, confirms these observations and indicates that polygenic Alzheimer’s disease risk (outside the APOE region) contributes to tau pathology in A+ participants but has no meaningful contribution in A− participants. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.