The APOE Gene Locus in Frontotemporal Dementia and Primary Progressive Aphasia | Dementia and Cognitive Impairment | JAMA Neurology | JAMA Network
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Original Contribution
May 2011

The APOE Gene Locus in Frontotemporal Dementia and Primary Progressive Aphasia

Author Affiliations

Author Affiliations: Geriatric Unit and Gerontology–Geriatric Research Laboratory, Department of Medical Sciences (Drs Seripa, Panza, and Pilotto), Unit of Biostatistics (Dr Pellegrini), Istituto Di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG); Institute of Neurology, Catholic University School of Medicine, Rome (Drs Bizzarro, Acciarri, and Masullo); and Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Santa Maria Imbaro (CH) (Dr Pellegrini), Italy.

Arch Neurol. 2011;68(5):622-628. doi:10.1001/archneurol.2011.90

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

Design  Case-control study.

Setting  Neurology clinic, Rome, Italy.

Patients  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.

Main Outcome Measures  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.

Results  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).

Conclusion  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.