Based on these two hypotheses, the negative association between frailty and AD documented by our study could depend on the fact that (1) in frailer patients, even low amounts of amyloid and tau (lower than the cutoffs used in clinical practice) may result in MCI, and/or (2) in frail patients, other pathophysiological mechanisms (beyond amyloid and tau) may play a central role in the pathogenesis of cognitive dysfunctions. The gene discussed is MAPT; the disease is Alzheimer disease.