GENETIC ASSOCIATION OF ALZHEIMER'S RISK VARIANT IN THE <i>PICALM</i> GENE WITH COGNITIVE-EVENT-RELATED POTENTIALS DURING AGING
Aging and genetic predisposition are the major risk factors for age-related neurodegenerative disorders including the most common Alzheimer's disease (AD). Genome-wide association studies (GWAS) have identified statistically significant association of PICALM rs3851179 with AD. The PICALM G allele appears to confer risk for AD, while the A allele is thought to have a protective effect. We examined the association of the PICALM rs3851179 polymorphism with the parameters of cognitive component P3 of auditory event-related potentials in 87 non-demented volunteers (age range 19-77 years) subdivided into cohorts of those younger and those older than 50 years of age. The homozygous presence of the AD risk variant PICALM GG was associated with an increase in the latency of the cognitive P3 component in the older cohorts. Age-dependent increase in the P3 component latency was significantly higher in the carriers of PICALM GG compared to PICALM AA& AG carriers. The results indicate more pronounced decline in cognitive processing speed in the PICALM GG carriers during aging and suggest age-related neuronal dysfunction and subclinical neurodegeneration in hippocampal and the fronto-parietal networks. Such changes are less pronounced in the carriers of the A PICALM allele, which may underlie the protective effect of this allele on the rate of cognitive decline and the risk of development of AD.