APOE and early-onset autosomal dominant Alzheimer disease: For example, a study on two large cohorts found that a PRS that included APOE ɛ4 predicted much more of the variance in Aβ-burden (∼8%–24%) than a PRS that excluded the APOE region (∼2%–4%).2 There is also support for the notion that APOE ɛ4 has little effect on downstream aspects of Alzheimer’s disease once Aβ-burden is accounted for.