APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD)

Sarju G. Mehta, Giles D.J. Watts, Jennifer L. Adamson, Mike Hutton, Geanie Umberger, Shuling Xiong, Sheena Ramdeen, Mark A. Lovell, Virginia E. Kimonis, Charles D. Smith

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P = 0.0002), myopathy (P = 0.0006), and age (P = 0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P = 0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalGenetics in Medicine
Issue number1
StatePublished - Jan 2007


  • Apolipoprotein-E
  • Frontotemporal dementia
  • Inclusion body myopathy
  • Muscular dystrophy
  • Paget's disease of bone
  • Valosin-containing protein

ASJC Scopus subject areas

  • Genetics(clinical)


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