TY  - JOUR
AU  - Chatterjee, Madhurima
AU  - Özdemir, Selcuk
AU  - Kunadt, Marcel
AU  - Koel-Simmelink, Marleen
AU  - Boiten, Walter
AU  - Piepkorn, Lars
AU  - Pham, Thang V
AU  - Chiasserini, Davide
AU  - Piersma, Sander R
AU  - Knol, Jaco C
AU  - Möbius, Wiebke
AU  - Mollenhauer, Brit
AU  - van der Flier, Wiesje M
AU  - Jimenez, Connie R
AU  - Teunissen, Charlotte E
AU  - Jahn, Olaf
AU  - Schneider, Anja
TI  - C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer's disease: A multi-cohort proteomics and immuno-assay validation study.
JO  - Alzheimer's and dementia
VL  - 19
IS  - 11
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2023-00459
SP  - 4828 - 4840
PY  - 2023
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: pathology
KW  - Complement C1q
KW  - Proteomics
KW  - Amyloid beta-Peptides: metabolism
KW  - Peptide Fragments: cerebrospinal fluid
KW  - Biomarkers: cerebrospinal fluid
KW  - Extracellular Vesicles: metabolism
KW  - tau Proteins: cerebrospinal fluid
KW  - Cognitive Dysfunction: cerebrospinal fluid
KW  - Complement C1q (NLM Chemicals)
KW  - Alzheimer's disease (AD) (Other)
KW  - biomarker (Other)
KW  - cerebrospinal fluid (CSF) (Other)
KW  - complement (Other)
KW  - extracellular vesicles (Other)
KW  - immune system (Other)
KW  - mild cognitive impairment (MCI) (Other)
KW  - proteomics (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37023079
DO  - DOI:10.1002/alz.13066
UR  - https://pub.dzne.de/record/257583
ER  -