MAPT and Alzheimer disease: However, it is essential to note that structural changes in hippocampal atrophy occur many years after the accumulation of beta-amyloid (Aβ) pathology in the brain (McKhann et al., 2011; Villemagne et al., 2013), and impairment of functional connections in AD can be detected almost synchronously with Aβ and tau measured using positron emission tomography (PET).