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- Title
Identifying genetic variants for amyloid b in subcortical vascular cognitive impairment.
- Authors
Hang-Rai Kim; Sang-Hyuk Jung; Beomsu Kim; Jaeho Kim; Hyemin Jang; Jun Pyo Kim; Kim, So Yeon; Duk L. Na; Hee Jin Kim; Kwangsik Nho; Hong-Hee Won; Sang Won Seo
- Abstract
Background: The genetic basis of amyloid b (Ab) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Ab deposition in patients with SVCI. Methods: We recruited a total of 110 patients with SVCI and 424 patients with Alzheimer's disease-related cognitive impairment (ADCI), who underwent Ab positron emission tomography and genetic testing. Using candidate ADassociated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Ab-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP). Results:We identified a novel SNP, rs4732728, which showed distinct associations with Ab positivity in patients with SVCI (Pinteraction = 1.49 x 10-5); rs4732728 was associated with increased Ab positivity in SVCI but decreased Ab positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Ab positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757-0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = -0.182, P = 0.005). Conclusion: The novel genetic variants associated with EPHX2 showed a distinct effect on Ab deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Ab positivity and a candidate therapeutic target for SVCI.
- Subjects
COGNITION disorders; ALZHEIMER'S disease; CONFIDENCE intervals; SINGLE nucleotide polymorphisms; MILD cognitive impairment; GENETIC variation; GENETIC testing; AMYLOID beta-protein precursor; GENE expression; POSITRON emission tomography; REPLICATION (Experimental design); GENOTYPES; DESCRIPTIVE statistics; RESEARCH funding; RECEIVER operating characteristic curves; NEURORADIOLOGY; LONGITUDINAL method; DISEASE complications
- Publication
Frontiers in Aging Neuroscience, 2023, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2023.1160536