ApoE Distribution and Family History in Genetic Prion Diseases in Germany
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We analyzed the ApoE genotype in patients with genetic prion diseases (gPD) with respect to family history (FH) of dementia/prion disease (PD) compared to non-demented controls. Fifty-nine gPD patients and 51 sex-/age-matched controls were included. A positive FH of dementia and PD (PFH) were evaluated. The prion protein gene (PRNP) codon 129 and ApoE genotype were determined by polymerase chain reaction (PCR). The frequency of FH of neurodegenerative disorder/prion disease/dementia varied in different PRNP mutations. PFH was found in 87% of D178N patients, but was rarer in others. Although the ApoE genotype distribution was not significantly different between gPD patients and controls, the protective E2 alleles were more frequent in controls than in patients without a PFH and even less frequent in those with a PFH (18, 16, and 11%). E4 alleles as a risk factor of Alzheimer’s disease were more common in controls and patients with a PFH than in those without PFH (25, 21, and 13%). No effect of the codon 129 genotype was detected. Only about two-thirds of gPD patients had PFH of PD, while in one-third, PFH of slowly progressive dementia was reported. Underreporting of PFH of gPD may play a role; however, the varying PFH frequency across various mutations is not explained by this factor only.
KeywordsApoE CJD Codon 129 genotype PRNP Dementia
We thank Ms. Bodemer, Ms. Ciesielczyk, Ms. Hartung, Ms. Henn, and Ms. Staniszewski for technical assistance. The assistance of Ms. Ehrlich is gratefully acknowledged. This study was supported by grants from the Federal Ministry of Health and Social Security (325-4471-02/15), the European Commission (QLG3-CT-2002-81606), and the Federal Ministry of Education and Research (01GI0301).
- Goldfarb, L. G., Brown, P., & Gajdusek, D. C. (1992).The molecular genetics of human transmissible spongiform encephalopathy. In S. B. Prusiner, J. Collinge, J. Powell, & B. Anderton (Ed.), Prion diseases of human and animals (pp. 139–153).Google Scholar
- O’Brien, J., Ames, D., & Burns, A. (2000). Dementia. London: Arnold.Google Scholar
- Raymond, M., & Rousset, F. (1995). Population genetics software for exact tests and ecumenicism. Journal of Heredity, 86, 248–249.Google Scholar
- Van Everbroeck, B., Green, A., Pals, P., Martin, J. J., & Cras, P. (1999). Decreased levels of amyloid-beta 1-42 in cerebrospinal fluid of Creutzfeldt–Jakob disease patients. Journal of Alzheimers Disease, 1, 419–424.Google Scholar
- WHO (1998). Human transmissible spongiform encephalopathies. Weekly Epidemiological Record, 47, 361–365.Google Scholar