APOE and Alzheimer disease: Important aspects of this model are bolstered by evidence that: (1) a gain-of-function variant in the RELN gene protects from familial, autosomal dominant AD in humans,[48, 49] (2) the DAB1 gene locus is associated with AD risk in APOE ε4 homozygotes,[50] and (3) a single-cell transcriptomics report suggesting that vulnerable neuron subpopulations have higher expression of RELN, DAB1 and LRP8 than less vulnerable neurons.[51] Altogether, these findings support the concept that disruption or compromised function of the ApoER2-Dab1 pathway could contribute to neurodegeneration in AD.