OBJECTIVE: The aim of our current research project is to further evaluate the role of risk factors in the pathogenesis of Alzheimer's disease; these include genetic variations, environmental factors and lifestyle issues. METHODS: We have been conducting an association study on 373 patients with Alzheimer's disease and 286 unrelated control individuals. The occurrence and the age of onset of diabetes and cardiovascular diseases were evaluated in both groups. Apolipoprotein E genotype was analyzed in all subjects by PCR method. RESULTS: We report that, in Czech population carrying ApoE4 allele increases risk of Alzheimer's disease 2.1-fold and genotype E4E4 increases the risk 8.4-fold. We have also identified a significant association between ApoE4 allele, Alzheimer's disease and hypertension. Hypertensive subjects with the ApoE4 allele have 1.5-fold greater risk of Alzheimer's disease. Thus, hypertension together with ApoE4 allele translates into 1.5-fold higher risk of AD. The most intriguing original finding in the present study is that Alzheimer's disease patients have significantly later onset of diabetes, hypertension and stroke in comparison with control subjects. This effect was not influenced by ApoE genotype. The diabetes appeared in AD patients on average more than 10 years later than in the control subjects (p<0.0001), hypertension was diagnosed 14 years later in AD patients (p<0.00001) and stroke occurred on average 6 years later (p<0.005), compared to the control group. CONCLUSIONS: Overall, in addition to the above novel findings, our study expands the data base on risk factors that could be used in near future when testing for the genetic risk of Alzheimer's disease.

Department of Epidemiology and Public Health Faculty of Medicine University of Ostrava Czech Republic

Discipline Anatomy and Histology and Bosch Institute School of Medical Sciences Sydney Medical School The University of Sydney NSW Australia

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic

Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease

Single Nucleotide Polymorphism rs11136000 of CLU Gene (Clusterin, ApoJ) and the Risk of Late-Onset Alzheimer's Disease in a Central European Population

CHAT gene polymorphism rs3810950 is associated with the risk of Alzheimer's disease in the Czech population