Genetic Association between Alzheimer’s Disease Risk Variant of the PICALM Gene and Auditory Event-Related Potentials in Aging

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N. V. Ponomareva^1,2,a*, T. V. Andreeva^2,3, M. A. Protasova², Yu. V. Filippova¹, E. P. Kolesnikova¹, V. F. Fokin¹, S. N. Illarioshkin¹, and E. I. Rogaev^2,3,4,b*

¹Research Center for Neurology, 125367 Moscow, Russia

²Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia

³Lomonosov Moscow State University, Department of Biology, Center of Genetics and Genetic Technologies, 119991 Moscow, Russia

⁴Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, USA

^* To whom correspondence should be addressed.

Received May 21, 2018; Revision received June 26, 2018

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Aging and genetic predisposition are major risk factors in age-related neurodegenerative disorders. The most common neurodegenerative disorder is Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified statistically significant association of the PICALM rs3851179 polymorphism with AD. The PICALM G allele increases the risk of AD, while the A allele has a protective effect. We examined the association of the PICALM rs3851179 polymorphism with parameters of the P3 component of auditory event-related potentials (ERPs) in 87 non-demented volunteers (age, 19-77 years) subdivided into two cohorts younger and older than 50 years of age. We found statistically significant association between the AD risk variant PICALM GG and increase in the P3 latency in subjects over 50 years old. The age-dependent increase in the P3 latency was more pronounced in the PICALM GG carriers than in the carriers of the PICALM AA and PICALM AG genotypes. The observed PICALM-associated changes in the neurophysiological processes indicate a decline in the information processing speed with aging due, probably, to neuronal dysfunction and subclinical neurodegeneration of the neuronal networks in the hippocampus and the frontal and parietal cortical areas. Such changes were less pronounced in the carriers of the PICALM gene A allele, which might explain the protective effect of this allele in the cognitive decline and AD development.

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KEY WORDS: PICALM genotype, neurodegeneration, aging, genetic predisposition, Alzheimer’s disease, event-related potentials, P300

DOI: 10.1134/S0006297918090092

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