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The apolipoprotein E 4 allele selectively increases the risk of frontotemporal lobar degeneration in males

¹ Clinical Neurosciences Research Group, University of Manchester, Manchester, UK
² Department of Neurology, Greater Manchester Neurosciences Centre, Hope Hospital, Manchester, UK
³ Centre for Integrated Genomic Medical Research, University of Manchester
⁴ Division of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA

Correspondence to:
Correspondence to:
Professor D M A Mann
Clinical Neurosciences Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Stott Lane, Salford M6 8HD, UK; david.mann{at}man.ac.uk

Objective: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent.

Methods: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE 4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex.

Results: The APOE 4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE 2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE 4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE 2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE 2 nor APOE 4 allele frequency varied significantly between any of the clinical subtypes.

Conclusions: In FTLD not associated with mutations in tau gene, possession of APOE 4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women.

Abbreviations: FTD, frontotemporal dementia; FTLD, frontotemporal lobar degeneration; MND, motor neurone disease

Keywords: frontotemporal lobar degeneration; apolipoprotein E gene; dementia; genetic risk; gender