A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease

Matthijs B de Geus; Angus C Nairn; Steven E Arnold; Becky C Carlyle

doi:10.1093/braincomms/fcaf202

journal article Open Access Jan 01, 2025

A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease

Matthijs B de Geus

Angus C Nairn Steven E Arnold Becky C Carlyle

Brain Communications Vol. 7 No. 3 · Oxford University Press (OUP)

View at Publisher Save 10.1093/braincomms/fcaf202

Abstract

Abstract
Alzheimer's disease is a multifaceted neurodegenerative disorder, with diverse underlying pathophysiological processes extending beyond amyloid-β and tau accumulation. The heterogeneity of Alzheimer's disease necessitates the identification of a broad array of biomarkers that capture the diverse mechanisms contributing to disease onset and progression. In this study, we systematically compiled and analysed cerebrospinal fluid proteomics data from omics studies utilizing mass spectrometry, Olink, or SomaScan platforms. Systematic literature searches for each platform revealed a total of 264 studies. From this, a set of 18 studies were selected based on sample size, number of markers analysed, and open data availability. We found a total of 1,448 differentially expressed proteins between Alzheimer's disease and amyloid negative controls across these datasets, with 635 being found in more than one study. A ‘top’ set of 61 differentially expressed proteins were consistently reported in at least six studies. Clustering and functional enrichment analysis of the top differentially expressed proteins indicated involvement in metabolic regulation, glutathione metabolism and proteins of the 14-3-3 family, reflecting importance of reactive oxygen species (ROS) response. Synaptic signalling processes were found to generally be downregulated. We further integrated the top differentially expressed proteins with results from a study on familial Alzheimer's disease cerebrospinal fluid to assess at which stage of disease progression these proteins change, highlighting markers shared between sporadic and familial Alzheimer's disease datasets. Lastly, we examine the overlap of the top differentially expressed proteins between cerebrospinal fluid and brain tissue using a publicly available database. This analysis provides a comprehensive overview of the Alzheimer's disease cerebrospinal fluid proteomic landscape, indicating changes in key pathways and cellular processes associated with Alzheimer's disease pathology. By integrating data from different platforms, we highlight reproducible protein changes that may serve as promising candidates for further biomarker research aimed at improving patient stratification, tracking disease progression, and assessing therapeutic interventions.

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Details

Published: Jan 01, 2025
Vol/Issue: 7(3)
License: View

Authors

M

Matthijs B de Geus

Department of Neurology, Massachusetts General Hospital , Charlestown, MA 02129 ,; Cell & Chemical Biology, Leiden University Medical Center , 2333ZC Leiden ,

A

Angus C Nairn

Department of Psychiatry , Yale University, New Haven, CT 06511 ,

S

Steven E Arnold

Department of Neurology, Massachusetts General Hospital , Charlestown, MA 02129 ,; Neurology, Harvard Medical School , Boston, MA 02115 ,

B

Becky C Carlyle

Department of Physiology Anatomy and Genetics, Oxford University , Oxford OX1 3PT ,; Kavli Institute for Nanoscience Discovery , Oxford OX1 3QU ,

Funding

Biomedical Research Centre

Cite This Article

Matthijs B de Geus, Angus C Nairn, Steven E Arnold, et al. (2025). A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease. Brain Communications, 7(3). https://doi.org/10.1093/braincomms/fcaf202

A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease

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