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 earl ier age at onset of dementia. Whether apo E epsilon 4 is a specific ri sk factor for Alzheimer's disease or is a more general susceptibility factor that shifts the age at onset of neurodegenerative diseases to e arlier ages is unknown. To test these possibilities, we determined the apolipoprotein E genotypes of subjects with familial or sporadic amyo trophic lateral sclerosis (ALS). ApoE allele frequencies of the apoE g ene 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 frequen cies of the general population. Furthermore, no significant associatio n 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 eps ilon 4 (sporadic ALS: n = 15, onset at 57.7 +/- 13.9 years; familial A LS: 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 with out epsilon 4 (sporadic ALS: n = 28, onset at 53.1 +/- 17.0 years; fam ilial 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 doe s not have a global effect on the pathogenesis of other neurodegenerat ive diseases.