APOE Alleles With Tau and A Pathology in Patients With Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex in the Kii Peninsula

Background and ObjectivesTo examine the association of the APOE epsilon 4 and epsilon 2 alleles with the pathologic features of patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex cases in the Kii peninsula of Japan (Kii ALS/PDC).MethodsWe analyzed APOE variants in 18 autopsy patients with ALS/PDC, consisting of 9, 8, and 1 patient with PDC, ALS, and PDC followed by ALS, respectively. Moreover, we revealed the relationship between APOE variants and A beta and tau pathologies.ResultsThe frequency of the epsilon 4 allele was not different between patients with Kii ALS/PDC and control participants. APOE epsilon 4 was associated with increased A beta pathology (p = 0.005 by the chi(2) test), but not with increased tau pathology (p = 0.984). The frequency of the epsilon 2 allele was apparently higher than that of control participants (p = 0.254). The APOE epsilon 2 allele was associated with increased tau pathology (p = 0.009) and not with reduced A beta pathology (p = 0.383) in patients with Kii ALS/PDC.DiscussionAlthough there was no overrepresentation of the frequency of the epsilon 4 or epsilon 2 allele, our findings suggest that the epsilon 2 allele is associated with increased tau pathology and not with reduced A beta pathology in patients with Kii ALS/PDC.