By definition individuals with preclinical AD are cognitively unimpaired (CU), however prospective studies show that preclinical AD is characterised by insidious and progressive cognitive decline (4, 5, 6) which accompanies the continued accumulation of amyloid and tau (7), loss of brain volume (8), reduced brain activity (9) and faster progression to symptomatic disease (10). The gene discussed is MAPT; the disease is Alzheimer disease.