Our main findings are that: (1) T1w and FLAIR signal variabilities are higher and the average FLAIR signal is lower as a function of disease progression in mutation carriers; (2) these MR signal changes occur, at least partly, independent from cortical atrophy and both within and outside the atrophy topography associated with dominantly inherited Alzheimer disease; and (3) closer to the AO, tau pathology was increasingly more important in driving the measured changes compared with amyloid pathology. The gene discussed is MAPT; the disease is Atrophy.