Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease. Issue 6 (2nd June 2020) - Bader, Jakob M
Abstract: Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems‐wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)‐based proteomics workflow for the in‐depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1, 000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature. Synopsis: A robust proteomic workflow quantifies more than 1, 000 proteins in cerebrospinal fluid and reveals an Alzheimer's Disease‐associated signature of more than 20 proteins across three independent cohorts. These include tau, superoxide dismutase 1, PARK7, YKL‐40 and novel biomarker candidates. Proteomics workflow for quantification of more than 1, 000 proteins from microliters of cerebrospinal fluid. More than 20 proteins consistently associated with Alzheimer's Disease across three cohorts comprising about 200 individuals in total. Alzheimer's Disease CSF signature of Tau, SOD1, PARK7, YKL‐40, and glycolysis‐related proteins. Abstract : A robust proteomic workflow quantifies more than 1, 000 proteins in cerebrospinal fluid and reveals an Alzheimer's Disease‐associated signature of more than 20 proteins across three independent cohorts. These include tau, superoxide dismutase 1, PARK7, YKL‐40 and novel biomarker candidates.