Intriguingly, Bracher-Smith et al.(72) recently reported a genetic association between the DAB1 locus and AD risk that was evident only in APOE4 homozygotes, a high-risk population that accounts ≈ 10% of sAD cases.(73) Our findings of extensive Dab1 accumulation in APOE3 homozygote and APOE2/APOE3 heterozygote MCI and sAD cases provide evidence that ApoER2-Dab1 disruption is a shared mechanism underlying sAD that may be exacerbated by, but is not dependent on, the APOE4 gene variant. This evidence concerns the gene LRP8 and Alzheimer disease.