The APOE gene locus in frontotemporal dementia and primary progressive aphasia

To investigate the role of the apolipoprotein E (APOE) locus in frontotemporal dementia (FTD) and primary progressive aphasia (PPA).

Case-control study.

Neurology clinic, Rome, Italy.

Eighty-six patients with a clinical diagnosis of sporadic FTD, including 32 patients with a clinical diagnosis of PPA, and 99 nondemented cognitively intact control subjects.

Genotype analysis of the 3 single-nucleotide polymorphisms rs449647, rs769446, and rs405509 in the promoter region of the APOE gene and of the 2 single-nucleotide polymorphisms rs429358 and rs7412 forming the common apoE polymorphism.

Significant associations with FTD were observed for genotypes rs449647 A/T (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.5), rs769446 T/C (OR, 4.4; 95% CI, 1.9-10.2), and APOE ε3/ε4 (OR, 4.1; 95% CI, 1.6-10.9). Significant associations with PPA were also observed for genotypes APOE ε3/ε4 (OR, 22.5; 95% CI, 1.2-229.4) and ε4/ε4 (OR, 7.5; 95% CI, 2.6-21.6). Significant associations with FTD were observed for haplotypes A-C-G-C-C (OR, 5.6; 95% CI, 1.4-21.5) and T-T-T-C-C (OR, 5.2; 95% CI, 1.1-24.0). Significant associations with PPA were also observed for haplotypes A-T-T-T-C (OR, 0.4; 95% CI, 0.2-0.9) and A-T-T-C-C (OR, 5.2; 95% CI, 1.4-19.3).

Although the physiological role of apoE in FTD and PPA needs further investigations, our results suggest an involvement of the APOE gene locus in the genetics of FTD and PPA.