MAPT and Alzheimer disease: However, later in life, the cognitive alterations in DS individuals are aggravated because their brains undergo premature aging and present the early appearance of Alzheimer’s disease (AD) neuropathology, which is characterized by amyloid plaque deposits, neurofibrillary tangles (NFTs) caused by hyperphosphorylation of the tau protein, neurodegeneration, synapse loss, and neuroinflammation due to microglial activation which increases the release of pro-inflammatory cytokines [4,10,11,12,13,14].