Cited by 382Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration

Mollenhauer, Brit, Cullen, Valerie, Kahn, Ilana, Krastins, Bryan, Outeiro, Tiago F., Pepivani, Imelda, Ng, Juliana, Schulz-Schaeffer, Walter, Kretzschmar, Hans A., McLean, Pamela J., Trenkwalder, Claudia, Sarracino, David A., VonSattel, Jean-Paul, Locascio, Joseph J., El-Agnaf, Omar M.A., Schlossmacher, Michael G.·2008·Experimental Neurology

DOI 10.1016/j.expneurol.2008.06.004

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Abstract

Because accumulation of alpha-synuclein (alphaS) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several alphaS-derived peptides by mass spectrometry. The concentration of alphaS amounted to <0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total alphaS levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF alphaS concentrations ranged from 0.8 to 16.2 pg/microl. Mean CSF alphaS values were lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF alphaS levels (n=8; mean, 300 pg/microl; p<0.001). Our results unequivocally confirm the presence of alphaS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF alphaS concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF alphaS resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies.

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Mollenhauer, 2006, Proteome analysis of cerebrospinal fluid by mass spectrometry: a platform for marker development in synucleinopathies, Movement Disorders, 21
Schlossmacher, 2006, Monitoring of alpha-synuclein steady-state levels in vivo by ELISA, Movement disorders, 21

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Authors: Mollenhauer, B., Cullen, V., Kahn, I., Krastins, B., Outeiro, T. F., Pepivani, I., Ng, J., Schulz-Schaeffer, W., Kretzschmar, H. A., McLean, P. J., Trenkwalder, C., Sarracino, D. A., VonSattel, J.-P., Locascio, J. J., El-Agnaf, O. M. A., & Schlossmacher, M. G.
Affiliations: Brigham and Women's Hospital (US)
Harvard University (US)
University of Ottawa (CA)
Ludwig-Maximilians-Universität München (DE)
Paracelsus Elena Klinik Kassel (DE)
Columbia University (US)
Corresponding author: Schlossmacher, Michael G.
ORCID: Mollenhauer, Brit
Kahn, Ilana
Outeiro, Tiago F.
McLean, Pamela J.
Trenkwalder, Claudia
Locascio, Joseph J.
Schlossmacher, Michael G.
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2008-10
Volume: 213
Issue: 2
Pages: 315-325
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1016/j.expneurol.2008.06.004
OpenAlex: W2003260773
Cited by: 382
References: 68
Citations by year: 2026: 6 · 2025: 18 · 2024: 8 · 2023: 9 · 2022: 22 · 2021: 16 · 2020: 25 · 2019: 19 · 2018: 16 · 2017: 17 · 2016: 20 · 2015: 25 · 2014: 32 · 2013: 26 · 2012: 30
FWCI: 19.25
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (P50NS038375, 5P50-NS038375)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: alpha-synuclein, cerebrospinal fluid, Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, Creutzfeldt-Jakob disease, synucleinopathies, cell-free biomarkers, ELISA quantification, neurodegeneration, prion disease, cell death
MeSH terms: Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Animals, Cells, Cultured, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Nerve Degeneration, Biomarkers, Mice, Rats, alpha-Synuclein

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Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration

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