APOE and early-onset autosomal dominant Alzheimer disease: Recent works have linked established Alzheimer’s disease risk loci outside APOE, such as CR1, to amyloid biomarker levels.23 Conversely, studies of biomarker levels of tau repeatedly highlight the APOE locus.23,24 However, if being A+ were a prerequisite to exhibit pathological accumulation of tau, then the strong genetic association with APOE in these GWASs would merely reflect the necessary condition rather than a genuine direct molecular process that affects tau levels.