MAPT and early-onset autosomal dominant Alzheimer disease: The “amyloid hypothesis” that small soluble oligomers of Aβ underlie the key phenotypic characteristics of Alzheimer's disease is supported by experimental data showing that these small soluble oligomers may (1) cause synaptic loss and decreased dendritic spine density; (2) cause hyperphosphorylation of tau proteins with resulting intraneuronal neurofibrillary tangles and collapse of the neuritic cytoskeleton; and (3) cause memory impairment and cognitive losses in the absence of amyloid plaques.