MAPT and Alzheimer disease: Importantly, the neuropathological underpinnings of Alzheimer’s disease—the accumulation of amyloid beta (Aβ) deposits and hyperphosphorylated tau (pTau) tangles in the brain—occur well before the onset of clinical manifestations (Sperling et al., 2011), with pTau accumulation occurring earlier, possibly decades prior to clinical cognitive decline (Braak and Del Tredici, 2011).