APOE and amyotrophic lateral sclerosis: For comparison, 90–95% of ALS and PD cases are sporadic, and known pathogenic variants explain only 10–20% of ALS and ~14% of PD susceptibility.7–10 Conversely, in late-onset AD, APOE ε4 is the strongest risk factor, and genome-wide association study (GWAS) identified variants collectively explain ~70% of disease susceptibility.11, 12