Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein
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+ (...
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Published in | Frontiers in aging neuroscience Vol. 15; p. 1273825 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Lausanne
Frontiers Research Foundation
26.10.2023
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Kristine Freude, University of Copenhagen, Denmark Reviewed by: Ravi Muddashetty, Indian Institute of Science, India; Eva Bagyinszky, Gachon University, Republic of Korea |
ISSN: | 1663-4365 1663-4365 |
DOI: | 10.3389/fnagi.2023.1273825 |