The only widely confirmed sporadic AD genetic risk factor is carrying the apolipoprotein E ε4 allele. The results of numerous studies on various other genes are highly inconclusive. Genetic studies in mild cognitive impairment (MCI) are scarce.

To assess the influence of APOE, CYP46, PRNP, PRND genetic polymorphisms on the risk of AD and MCI.

To date, over 100 subjects with AD, amnestic form of MCI and cognitively healthy age-matched controls have been recruited for the study (ongoing recruitment). To increase the homogeneity of the studied population subjects with prominent comorbid vascular risk factors, family history of dementia or satisfying criteria for non-AD neurodegenerative dementias have been excluded from the study. RFLP and sequencing techniques were employed to assess polymorphic sites in the CYP46, PRNP, PRND and APOE genes.

As expected, the proportion of APOE ε4 carriers was significantly higher in the AD group compared to controls. No statistically significant influence of polymorphisms in the CYP46, PRNP and PRND genes on the risk of AD or MCI was observed. However, the odds ratio for PRNP codon 129 homozygosity was over fivefold higher in the AD group compared to other study groups.

The significance of APOE genotype as an AD risk factor seems to be beyond controversy. The role of other genes putatively involved in the pathobiology of neurodegenerative disorders seems vague at most. Studies on much larger populations are required to estimate true significance of those genetic variants in the etiology of AD.