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 A131-42 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 x 10-5). Further, the rs5848 SNP status was associated with increased CSF tau protein-a marker of neurodegeneration (p = 0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies. (C) 2017 Elsevier Inc. All rights reserved.