This scientific commentary refers to ‘Distinct brain pathologies associated with Alzheimer’s disease biomarker-related phospho-tau 181 and phospho-tau 217 in App knock-in mouse models of amyloid-β amyloidosis’ by Hirota et al. (https://doi.org/10.1093/braincomms/fcac286) and ‘Predictive blood biomarkers and brain changes associated with age-related cognitive decline’ by Saunders et al. (https://doi.org/10.1093/braincomms/fcad113). The gene discussed is MAPT; the disease is early-onset autosomal dominant Alzheimer disease.