Journal Article DZNE-2023-00459

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

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2023
Wiley Hoboken, NJ

Alzheimer's and dementia 19(11), 4828 - 4840 () [10.1002/alz.13066]

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Abstract: 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.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).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).EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Complement C1q (MeSH) ; Proteomics (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Peptide Fragments: cerebrospinal fluid (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Extracellular Vesicles: metabolism (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Cognitive Dysfunction: cerebrospinal fluid (MeSH) ; Complement C1q ; Alzheimer's disease (AD) ; biomarker ; cerebrospinal fluid (CSF) ; complement ; extracellular vesicles ; immune system ; mild cognitive impairment (MCI) ; proteomics ; Amyloid beta-Peptides ; Peptide Fragments ; Biomarkers ; tau Proteins

Classification:

Contributing Institute(s):
  1. Translational Dementia Research (Bonn) (AG Schneider)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023
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Medline ; Creative Commons Attribution-NonCommercial CC BY-NC 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2023-04-20, last modified 2024-08-26