Evaluation of the Polygenic Risk Score for Alzheimer’s Disease in Russian Patients with Dementia Using a Low-Density Hydrogel Oligonucleotide Microarray
The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer’s disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed t...
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| Veröffentlicht in: | International journal of molecular sciences 2023-10, Vol.24 (19), p.14765 |
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| creator | Ikonnikova, Anna Morozova, Anna Antonova, Olga Ochneva, Alexandra Fedoseeva, Elena Abramova, Olga Emelyanova, Marina Filippova, Marina Morozova, Irina Zorkina, Yana Syunyakov, Timur Andryushchenko, Alisa Andreuyk, Denis Kostyuk, Georgy Gryadunov, Dmitry |
| description | The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer’s disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions. |
| doi_str_mv | 10.3390/ijms241914765 |
| format | Article |
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The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms241914765</identifier><identifier>PMID: 37834213</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Advertising executives ; Alzheimer's disease ; Apolipoproteins ; Cerebrospinal fluid ; Dementia ; Development and progression ; Disease prevention ; Ethylenediaminetetraacetic acid ; Genetic aspects ; Genetic testing ; Health risk assessment ; Hydrogels ; Medical research ; Medicine, Experimental ; Pathogenesis ; Regression analysis ; Risk factors</subject><ispartof>International journal of molecular sciences, 2023-10, Vol.24 (19), p.14765</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.</description><subject>Advertising executives</subject><subject>Alzheimer's disease</subject><subject>Apolipoproteins</subject><subject>Cerebrospinal fluid</subject><subject>Dementia</subject><subject>Development and progression</subject><subject>Disease prevention</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Genetic aspects</subject><subject>Genetic testing</subject><subject>Health risk assessment</subject><subject>Hydrogels</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Pathogenesis</subject><subject>Regression analysis</subject><subject>Risk 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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Advertising executives Alzheimer's disease Apolipoproteins Cerebrospinal fluid Dementia Development and progression Disease prevention Ethylenediaminetetraacetic acid Genetic aspects Genetic testing Health risk assessment Hydrogels Medical research Medicine, Experimental Pathogenesis Regression analysis Risk factors |
| title | Evaluation of the Polygenic Risk Score for Alzheimer’s Disease in Russian Patients with Dementia Using a Low-Density Hydrogel Oligonucleotide Microarray |
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