According to the NIA-AA research framework [2], individuals with evidence of Aβ pathology are on the Alzheimer’s disease continuum, while Aβ-negative (Aβ−) individuals who have abnormal tau and/or neurodegeneration have been regarded as harboring non-Alzheimer’s pathologic change (also known as suspected non-Alzheimer’s pathophysiology or SNAP). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.