APOLIPOPROTEIN-E GENOTYPING IN SPORADIC AMYOTROPHIC-LATERAL-SCLEROSIS- EVIDENCE FOR A MAJOR INFLUENCE ON THE CLINICAL PRESENTATION AND PROGNOSIS

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuro n disorder of unknown etiology. Recently, in Alzheimer's disease (AD) apolipoprotein E (APOE) alleles have been shown to play an important r ole in disease phenotype. To determine whether APOE have a similar inf luence in other neurodegenerative disorders, we studied APOE genotypes in 130 sporadic ALS patients, compared with controls. We also analyze d APOE genotypes regarding ALS clinical criteria. The frequency of APO E genotypes was not different between ALS and controls. However, subje cts with the APOE2/E3 genotype showed a significantly longer duration of the disease: 51 months vs. 28.5 for APOE3/E3 and 27.5 for APOE3/E4 (p = 0.001 and p = 0.02, respectively). There was a significantly high er proportion of bulbar ALS patients in the APOE3/E4 group (72% of the cases), whereas 90% of patients in the APOE2/E3 group showed limb ons et(p = 0.01). Ln the bulbar group, patients with APOE4 showed earlier onset of the disease: 60 vs. 66 years (mean age, p = 0.05). These resu lts are consistent with a protective role of APOE2 and a deleterious r ole of APOE4 in ALS as already found for AD. This parallel supports th e idea of a general role of APOE in neuronal degeneration or regenerat ion rather than a specific role in ALS or AD etiopathogenesis.