Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Autor:	Kashtanova DA; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Mamchur AA; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Dzhumaniyazova IH; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Ivanov MV; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Erema VV; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Zelenova EA; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Yakovchik AY; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Gusakova MS; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Rumyantseva AM; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Terekhov MV; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Matkava LR; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Akopyan AA; Russian Clinical Research Center for Gerontology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow, Russia., Strazhesko ID; Russian Clinical Research Center for Gerontology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow, Russia., Yudin VS; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Makarov VV; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Kraevoy SA; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia., Tkacheva ON; Russian Clinical Research Center for Gerontology, Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow, Russia., Yudin SM; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks', Federal Medical Biological Agency, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in aging neuroscience [Front Aging Neurosci] 2023 Oct 26; Vol. 15, pp. 1273825. Date of Electronic Publication: 2023 Oct 26 (Print Publication: 2023).
DOI:	10.3389/fnagi.2023.1273825
Abstrakt:	Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ ( n  = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Kashtanova, Mamchur, Dzhumaniyazova, Ivanov, Erema, Zelenova, Yakovchik, Gusakova, Rumyantseva, Terekhov, Matkava, Akopyan, Strazhesko, Yudin, Makarov, Kraevoy, Tkacheva and Yudin.)
Databáze:	MEDLINE
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