Proteome Profiling in Cerebrospinal Fluid Reveals Novel Biomarkers of Alzheimer's Disease

Overview

Journal Mol Syst Biol

Specialty Molecular Biology

Date 2020 Jun 3

PMID 32485097

Citations 116

Authors

Jakob M Bader

Philipp E Geyer

Johannes B Muller

Maximilian T Strauss

Manja Koch

Frank Leypoldt

Peter Koertvelyessy

Daniel Bittner

Carola G Schipke

Enise I Incesoy

Oliver Peters

Nikolaus Deigendesch

Mikael Simons

Majken K Jensen

Henrik Zetterberg

Matthias Mann

Affiliations

Soon will be listed here.

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.

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