Evaluation of the Polygenic Risk Score for Alzheimer’s Disease in Russian Patients with Dementia Using a Low-Density Hydrogel Oligonucleotide Microarray

Autor: Anna Ikonnikova, Anna Morozova, Olga Antonova, Alexandra Ochneva, Elena Fedoseeva, Olga Abramova, Marina Emelyanova, Marina Filippova, Irina Morozova, Yana Zorkina, Timur Syunyakov, Alisa Andryushchenko, Denis Andreuyk, Georgy Kostyuk, Dmitry Gryadunov
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14765 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms241914765
Popis: 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.
Databáze: Directory of Open Access Journals
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