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The influence of polygenic risk values on the development of dementia and on the dynamics of cognitive functions in patients with varying degrees of cognitive decline.
https://doi.org/10.25557/2073-7998.2025.12.154-156
Abstract
Patients with mild cognitive impairment (MCI) are at high risk of disease progression to Alzheimer’s disease (AD). Identifying genetic risk factors, such as the ε4 allele of the APOE gene, biomarkers corresponding to the early stages of AD, and assessing polygenic risk (PRS) with the potential for further stratification of patients into risk groups, may aid in predicting disease progression and prevention. The aim of this study is to develop a molecular method for analyzing genetic markers to assess the impact of polygenic risk values on the development of dementia and the dynamics of cognitive functions in patients with varying degrees of cognitive decline. A biochip was developed for the analysis of 21 risk markers and the ε2/ε3/ε4 alleles of the APOE gene. PRS values corresponding to the fourth quartile, as well as the presence of APOE-ε4, showed a significant association with an increased risk of developing dementia. PRS positively correlated with tTau and pTau181 and negatively correlated with the Aβ42/Aβ40 ratio. APOE-ε4 carriers had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/ Aβ40. Concentrations of IP-10, FGF-2, and VEGF were significantly associated with the APOE genotype. Patients with the APOE ε4/ε4 genotype exhibited lower baseline cognitive scores and negative cognitive dynamics. The lack of a significant association between PRS and cognitive function dynamics may be due to timely provision of appropriate medical care for the prevention of cognitive impairments.
Keywords
dementia,
Alzheimer’s disease,
neurodegeneration,
mild cognitive decline,
polygenic risk,
biochip,
single nucleotide polymorphisms,
genetic markers
Supporting agencies: This research was funded by the Moscow Centre for Innovative Technologies in Healthcare (Agreement No. 0803-4/23-1NIR).
About the Authors
E. D. Fedoseeva
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
A. Yu. Ikonnikova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
M. A. Emelyanova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
O. V. Antonova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
M. A. Filippova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
I. O. Morozova
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
A. B. Berdalin
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
V. M. Ushakova
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
A. G. Zeltser
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
T. S. Syunyakov
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
N. G. Osipova
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
Y. A. Zorkina
Mental Health Clinic No. 1 named after N.A. Alekseev; V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology
Russian Federation
Russian Federation
O. V. Abramova
Mental Health Clinic No. 1 named after N.A. Alekseev; V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology
Russian Federation
Russian Federation
D. S. Andreuyk
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
A. G. Ochneva
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
K. A. Pavlov
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
V. B. Savilov
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
K. P. Soloveva
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
M. V. Kurmishev
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
O. A. Karpenko
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
A. V. Andryushchenko
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
G. P. Kostyuk
Mental Health Clinic No. 1 named after N.A. Alekseev
Russian Federation
Russian Federation
A. Yu. Morozova
Mental Health Clinic No. 1 named after N.A. Alekseev; V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology
Russian Federation
Russian Federation
D. A. Gryadunov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Russian Federation
Russian Federation
References
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Review
For citations:
Fedoseeva E.D., Ikonnikova A.Yu., Emelyanova M.A., Antonova O.V., Filippova M.A., Morozova I.O., Berdalin A.B., Ushakova V.M., Zeltser A.G., Syunyakov T.S., Osipova N.G., Zorkina Y.A., Abramova O.V., Andreuyk D.S., Ochneva A.G., Pavlov K.A., Savilov V.B., Soloveva K.P., Kurmishev M.V., Karpenko O.A., Andryushchenko A.V., Kostyuk G.P., Morozova A.Yu., Gryadunov D.A. The influence of polygenic risk values on the development of dementia and on the dynamics of cognitive functions in patients with varying degrees of cognitive decline. Medical Genetics. 2025;24(12):154-156. (In Russ.) https://doi.org/10.25557/2073-7998.2025.12.154-156
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