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 <i>PICALM</i> rs3851179 with AD. The <i>PICALM G</i> allele appears to confer risk for AD, while the A allele is thought to have a protective effect. We examined the association of the <i>PICALM</i> 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 <i>PICALM GG</i> 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 <i>PICALM GG</i> compared to <i>PICALM AA& AG</i> carriers. The results indicate more pronounced decline in cognitive processing speed in the <i>PICALM GG</i> 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 <i>A PICALM</i> allele, which may underlie the protective effect of this allele on the rate of cognitive decline and the risk of development of AD.