MAPT and Alzheimer disease: Although these insoluble aggregates are classical histopathological hallmarks of AD, a substantial body of evidence indicates that soluble oligomeric forms of Aβ (AβOs) and tau (TauOs) are the most neurotoxic forms, inducing brain oxidative stress, mitochondrial damage, deregulation of intracellular signaling pathways, synapse failure and memory deficits.112 The key histological findings in AD encompass the accumulation of amyloid precursor protein (APP) and its cleavage into amyloid beta by β-site APP-cleaving enzyme 1 (BACE1).