APOLIPOPROTEIN-E EPSILON-4 ALLELE IS NOT ASSOCIATED WITH EARLIER AGE AT ONSET IN AMYOTROPHIC-LATERAL-SCLEROSIS

Apolipoprotein E allele 4 (ape E epsilon 4) is known to be in genetic disequilibrium with Alzheimer's disease and is associated with an earlier age at onset of dementia. Whether apo E epsilon 4 is a specific risk factor for Alzheimer's disease or is a more general susceptibility factor that shifts the age at onset of neurodegenerative diseases to earlier ages is unknown. To test these possibilities, we determined the apolipoprotein E genotypes of subjects with familial or sporadic amyotrophic lateral sclerosis (ALS). ApoE allele frequencies of the apoE gene of the ALS subjects (n = 170, epsilon 2 = 0.071, epsilon 3 = 0.771, epsilon 4 = 0.159) were found to be comparable to the allele frequencies of the general population. Furthermore, no significant association was observed between the age at onset or the duration of ALS and the inheritance of apoE epsilon 4: subjects with at least one copy of epsilon 4 (sporadic ALS: n = 15, onset at 57.7 +/- 13.9 years; familial ALS: n = 23, onset at 53.6 +/- 9.5 years, duration [n = 14] of 2.6 +/- 1.6 years) had comparable ages at onset and durations to subjects without epsilon 4 (sporadic ALS: n = 28, onset at 53.1 +/- 17.0 years; familial ALS: n = 56, onset at 50.8 +/- 12.1 years, duration [n = 30] of 1.9 +/- 0.8 years). The lack of association of apoE epsilon 4 with the age at onset and the duration of ALS suggests that apoE epsilon 4 does not have a global effect on the pathogenesis of other neurodegenerative diseases.