Despite inconsistent reports of ApoE’s role in ALS, it is possible that the ApoE-4 allele is a genetic risk factor and the ApoE-2 allele is a genetic protective factor for disease development, similar to the situation with Alzheimer’s disease (for review, see Serrano-Pozo et al., 2021). Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.