MAPT and early-onset autosomal dominant Alzheimer disease: Preclinical and clinical evidence demonstrate that soluble Aβ oligomers, instead of insoluble aggregates (plaques and fibrils), propagate neurotoxicity and disease progression in Alzheimer’s disease.14 The upstream role of Aβ in driving the tau pathology and cognitive deterioration in patients with Alzheimer’s disease is reinforced by longitudinal Aβ and tau PET imaging studies.