With these, we concluded that the APOEε4-imposed abnormal tau accumulation was associated with, yet not dependent of Aβ load, and future studies designed to understand the mechanisms by which APOE contributes to or counteracts Alzheimer’s disease pathogenesis via Aβ-dependent and Aβ-independent pathways is critical. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.