This scientific commentary refers to ‘Distinct brain pathologies associated with Alzheimer’s disease biomarker-related phospho-tau 181 and phospho-tau 217 inAppknock-in mouse models of amyloid-β amyloidosis’ by Hirotaet al.(https://doi.org/10.1093/braincomms/fcac286) and ‘Predictive blood biomarkers and brain changes associated with age-related cognitive decline’ by Saunderset al. (https://doi.org/10.1093/braincomms/fcad113).