APOE and Alzheimer disease: As already found for AD, inheritance of APOE alleles is associated with differences in the clinical course of ALS (with a protective role of E2 allele and a deleterious role of E4 allele) suggesting a potential implication of APOE genotype as a biomarker to discriminate clinical efficacy in ALS clinical trials (Moulard et al., 1996; Lacomblez et al., 2002; Li et al., 2004).