C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer’s disease: A multi-cohort proteomics and immuno-assay validation study

Authors

Chatterjee M, Özdemir S, Kunadt M, Koel-Simmelink M, Boiten W, Piepkorn L, Pham TV, Chiasserini D, Piersma SR, Knol JC, Möbius W, Mollenhauer B, van der Flier WM, Jimenez CR, Teunissen CE, Jahn O, Schneider A

Journal

Alzheimer’s & Dementia: The Journal of the Alzheimers Association

Citation

Alzheimers Dement. 2023 Apr 6.

Abstract

Introduction: Extracellular vesicles (EVs) may propagate and modulate Alzheimer’s disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs to identify proteins and pathways altered in AD.
Methods: CSF EVs were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide (Cohort 2) from non-neurodegenerative controls (n = 15, 16) and AD patients (n = 22, 20, respectively). EVs were subjected to untargeted quantitative mass spectrometry-based proteomics. Results were validated by enzyme-linked immunosorbent assay (ELISA) in Cohorts 3 and 4, consisting of controls (n = 16, n = 43, (Cohort3, Cohort4)), and patients with AD (n = 24, n = 100).
Results: We found > 30 differentially expressed proteins in AD CSF EVs involved in immune-regulation. Increase of C1q levels in AD compared to non-demented controls was validated by ELISA (∼ 1.5 fold, p (Cohort 3) = 0.03, p (Cohort 4) = 0.005).
Discussion: EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.

DOI

10.1002/alz.13066
 
Pubmed Link