CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN. Exp Gerontol. 2017 Feb 09;: Authors: Fardo DW, Katsumata Y, Kauwe JS, Deming Y, Harari O, Cruchaga C, Alzheimer's Disease Neuroimaging Initiative, Nelson PT Abstract OBJECTIVE: Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults.We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). METHODS: Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454).For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes. RESULTS: The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p<0.05 after Bonferroni correction).The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10(-5)).Further,...
Source: Experimental Gerontology - Category: Geriatrics Authors: Tags: Exp Gerontol Source Type: research