It is noteworthy that individuals with the PPP2R2B susceptibility allele in this study displayed significantly higher levels of tau and clinical impairment despite having no or marginally significant differences with their counterparts in age, sex, education, cerebrovascular disease risk, APOE ɛ4 status, and brain amyloid burden, supporting the concept that tau-associated genetic variation may impact clinically-relevant Alzheimer’s disease pathophysiology independently from other Alzheimer’s disease dementia-associated risk factors. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.