MAPT and early-onset autosomal dominant Alzheimer disease: In Alzheimer’s disease, oligomeric and aggregated neurofibrillary tau tangles are a major determinant of synaptic/cell dysfunction and death (Goedert et al., 1988; Ballatore et al., 2007; de Calignon et al., 2012), notwithstanding the importance of amyloid-β in its ‘toxic alliance’ with pathological tau (Bloom, 2014).