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Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration
Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, Ng J, Schulz-Schaeffer W et al.. Experimental neurology, 2008-06-14
Topic: Brain proteins, microglia and lab models
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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APA 7th
Mollenhauer, B., Cullen, V., Kahn, I., Krastins, B., Outeiro, T. F., Pepivani, I., et al. (2008). Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Experimental neurology. https://doi.org/10.1016/j.expneurol.2008.06.004
Vancouver
Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, et al. Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Experimental neurology. 2008. doi:10.1016/j.expneurol.2008.06.004. PMID: 18625222.
BibTeX
@article{mollenhauer2008-18625222,
author = {Mollenhauer, B. and Cullen, V. and Kahn, I. and Krastins, B. and Outeiro, T. F. and Pepivani, I. and Ng, J. and Schulz-Schaeffer, W. and others},
title = {{Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration}},
journal = {Experimental neurology},
year = {2008},
doi = {10.1016/j.expneurol.2008.06.004},
pmid = {18625222},
url = {https://doi.org/10.1016/j.expneurol.2008.06.004}
}
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Key findings
- 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.
- Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies.
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Study details
- Study designcross-sectional
- Participants57
- Effect size0.001%
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 57 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18625222) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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