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, Janet; Schulz‐Schaeffer, Walter; Kretzschmar, Hans A.; McLean, Pamela J.; Trenkwalder, Claudia; Sarracino, David; Vonsattel, Jean Paul; Locascio, Joseph J.; El‐Agnaf, Omar M. A.; Schlossmacher, Michael G.

doi:10.1016/j.expneurol.2008.06.004

Cited by 355 publications

(347 citation statements)

References 65 publications

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“…6C; PD 0.42 Ϯ 0.16; control 0.53 Ϯ 0.13). Thus, the TR-FRET assay platform was highly suitable for quantification of ␣-synuclein in human CSF while at the same time replicating the trend of reduced ␣-synuclein content in patients with typical PD (15)(16)(17)(18)21).…”

Section: Figure 3 Determination Of ␣-Synuclein Tr-fret Assay Specifimentioning

confidence: 81%

“…Protein concentration was determined by BCA assay (Pierce). Human CSF was collected by routine lumbar puncture into serial polypropylene tubes, as previously described (15), followed by the addition of protease inhibitors and 0.2% Nonidet P-40 before storage. For TR-FRET analysis, 1% TritonX-100 was added to CSF.…”

Section: Methodsmentioning

confidence: 99%

“…However, among these reports there are inconsistencies in both the reported absolute concentration of CSF ␣-synuclein and the putative nature of its change in the PD condition. Indeed, although some studies found reduced CSF ␣-synuclein in PD relative to controls (15)(16)(17)(18)(19), another reported no change (20). There is further disparity in findings comparing CSF ␣-synuclein in PD and synucleinopathies to that of other neurodegenerative disorders (16, 20 -24).…”

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

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Novel One-step Immunoassays to Quantify α-Synuclein

Bidinosti

Shimshek

Mollenhauer

et al. 2012

Journal of Biological Chemistry

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Background: Robust assays for ␣-synuclein quantification are essential for Parkinson disease therapeutic development. Results: TR-FRET immunoassays were validated for total and oligomeric ␣-synuclein and used to screen small molecules and kinases that regulate ␣-synuclein expression. Conclusion: TR-FRET immunoassays are suitable for biomarker development and high-throughput screening. Significance: This is the first platform for large-scale drug discovery and for neuronal pathway analysis of ␣-synuclein expression regulation.

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Section: Figure 3 Determination Of ␣-Synuclein Tr-fret Assay Specifimentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

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Novel One-step Immunoassays to Quantify α-Synuclein

Bidinosti

Shimshek

Mollenhauer

et al. 2012

Journal of Biological Chemistry

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“…The measurement of a‐syn concentrations in CSF by ELISAs has been proposed as a biomarker for a‐syn‐related disorders. However, despite many studies showing a reduction in CSF a‐syn levels in PD and in DLB,4, 6 overall results are not consistent 7. Even in those studies where a reduction in CSF a‐syn has been demonstrated, the differences are small8 and there is considerable overlap within patient groups and between patient and control groups.…”

Section: Introductionmentioning

confidence: 97%

“…The presence of a‐syn has been detected in biological fluids such as cerebrospinal fluid (CSF)4 and serum 5. The measurement of a‐syn concentrations in CSF by ELISAs has been proposed as a biomarker for a‐syn‐related disorders.…”

Section: Introductionmentioning

confidence: 99%

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Fairfoul

McGuire

Pal

et al. 2016

Ann Clin Transl Neurol

394

253

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We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.

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