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CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease
KTH Royal Inst Technol, SciLifeLab, Affin Prote, Stockholm, Sweden..
KTH Royal Inst Technol, SciLifeLab, Affin Prote, Stockholm, Sweden..
Karolinska Inst, Dept Neurosci, SciLifeLab, Stockholm, Sweden..
KTH Royal Inst Technol, SciLifeLab, Affin Prote, Stockholm, Sweden..
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2016 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 10, no 12, p. 1242-1253Article in journal (Refereed) Published
Abstract [en]

Purpose: This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such proteins and different neurodegenerative diseases.

Experimental design: Here 280 brain-enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach.

Results: Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease-associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling.

Conclusions and clinical relevance: These findings indicate that analyzing the brain-enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.

Place, publisher, year, edition, pages
2016. Vol. 10, no 12, p. 1242-1253
Keyword [en]
Alzheimer's disease, Cerebrospinal fluid, Neurogranin, Neuromodulin, Neuroproteomics
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-312660DOI: 10.1002/prca.201500150ISI: 000389221400009OAI: oai:DiVA.org:uu-312660DiVA, id: diva2:1064611
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceVINNOVAKnut and Alice Wallenberg FoundationSwedish Foundation for Strategic Research
Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2017-11-29Bibliographically approved

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