MAPT and hippocampal atrophy: Shortly after the accumulation of the first amyloid plaques, intracellular aggregation of hyperphosphorylated tau (p-Tau) forming neurofibrillary tangles (NFTs) begins, eventually leading to a Braak stage of V-VI in most individuals with DS, along with additional co-pathologies including neuronal loss, activation of glial cells, and hippocampal atrophy [10].