PROTEOMICS IDENTIFICATION OF NOVEL CEREBROSPINAL FLUID BIOMARKER CANDIDATES OF DEMENTIA WITH LEWY BODIES

Abstract

Cerebrospinal fluid (CSF) is considered an optimal source for the discovery of in vivo biomarkers for Dementia with Lewy bodies (DLB). Thus far, no reliable biomarker with both high sensitivity and specificity is available for DLB. CSF biomarkers could improve the early diagnostic accuracy, monitor disease progression and treatment response. We set out a proteomics study to identify novel CSF biomarker candidates for DLB. An in-depth proteomics workflow involving immune-depletion of high-abundant proteins, mono-dimensional SDS-PAGE in conjunction with nanoLC-MS/MS-based proteomics, database searching (MaxQuant) and label-free protein quantification was applied on CSF of 20 probable DLB patients and age and gender matched individuals with subjective cognitive decline (SCD, n=20). DLB patients had an abnormal (123)I-FP-CIT SPECT scan and normal CSF values of Aβ42, total tau and phosphorylated tau. Candidate biomarkers were selected based on the following criteria: (1) p<0.05, fold change>1.2, median normalized spectral count ≥2; (2) ≥50% separation between the two groups; and (3) identified peptide sequences covering ≥20% of the protein. Fifty-seven out of 2100 identified proteins were differentially expressed in DLB patients compared to SCD (p<0.05). 35 proteins were down-regulated and 22 proteins were up-regulated in DLB compared to SCD. We selected three proteins for validation by ELISA in a cohort including DLB, AD, Parkinson's disease (PD) and SCD. This validation is currently in progress. Our proteomics analysis of CSF identified several novel potential candidate biomarkers for DLB. Further validation of prioritized candidates in larger cohorts should delineate their potential as early diagnostic and/or progression biomarkers for DLB.