MAPT and Alzheimer disease: An imbalance between production and clearance of Aβ occurs early in AD and is typically followed by the accumulation of tau protein tangles (another key pathological hallmark of AD) and neurodegeneration detectable on brain magnetic resonance imaging (MRI) scans (Hardy and Selkoe, 2002; Sperling et al., 2011a; Jack et al., 2016).