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 epsilon 4 allele of the APOE gene (APOE-epsilon 4), 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 epsilon alleles of the APOE gene. This case-control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-beta (A beta) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-epsilon 4 were significant genetic risk factors for dementia. Adjusted for APOE-epsilon 4, 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-epsilon 4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with A beta 42/A beta 40 ratio. Carriers of APOE-epsilon 4 had higher levels of tTau and pTau181 and lower levels of A beta 42 and A beta 42/A beta 40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.