Combined Effects of Alzheimer Risk Variants in theCLUandApoEGenes on Ventricular Expansion Patterns in the Elderly

• DOI: 10.1523/jneurosci.5236-13.2014
• Publication Date: 2014-05-07T17:38:19Z
• Authors: Florence F. Rouss...; Boris A. Gutman; Sarah K. Madsen; John B. Colby; Paul M. Thompson
• Keywords: Clusterin; Apolipoprotein E; Genome-wide Association Study

The C allele at the rs11136000 locus in clusterin (CLU) gene is third strongest known genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent genome-wide association study of LOAD found evidence with CLU rs1532278, high linkage disequilibrium rs11136000. Brain structure and function are related to alleles, not just patients but also healthy young adults. We tracked volume lateral ventricles across baseline, 1-year, 2-year follow-up scans a large sample elderly human participants (N = 736 baseline), from Disease Neuroimaging Initiative, determine whether these variants predicted longitudinal ventricular expansion. major allele-previously linked reduced expression increased dementia-predicted faster expansion, independently dementia status or ApoE genotype. Further analyses revealed that had combined effects on both volumetric expansion ventricle surface morphology. rs1532278 strongly resembles regulatory element. Its was slightly stronger than our analyses, suggesting it may be closer functional variant. Clusterin affects inflammation, immune responses, amyloid clearance, which turn result neurodegeneration. Pharmaceutical agents such as valproate, counteract genetically determined expression, help achieve neuroprotection contribute prevention dementia, especially carriers variants.