Taken together, these possibilities suggest that there may be two basic subtypes of pathology progression in Alzheimer’s disease: an ‘amyloid-first’ variant, in which widespread Aβ plaques precede neocortical NFTs, and a ‘tau-first’ variant, in which early neocortical NFTs precede widespread Aβ. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.