Alpha‐synuclein RT ‐Qu IC in the CSF of patients with alpha‐synucleinopathies
Open accessAbstract
We have developed a novel real‐time quaking‐induced conversion RT ‐Qu IC ‐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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SAA has already proven to be a robust technique for identifying pathological α-synuclein from cerebrospinal fluid sample from patients with PD and RBD.
“SAA has already proven to be a robust technique for identifying pathological α-synuclein from cerebrospinal fluid sample from patients with PD and RBD [71, 72].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [71]
The Results report positive CSF RT-QuIC responses in 19 of 20 patients with PD and all three patients with RBD. The Discussion describes the RBD finding as suggestive and calls for validation in a larger cohort, so the claim that the technique is already proven robust for RBD overstates this paper's evidence. Page numbers were not provided in our copy. (LLM, conf=0.88)
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Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · cited 1× · see citing works
“All cases used had been examined histologically and the diagnosis reached using internationally accepted criteria.(18) Initial 10% w/v brain homogenates were prepared using phosphate-buffered saline (PBS) containing 1 mmol/L EDTA, 150 mmol/L NaCl, 0.”
MethodMollenhauer, B., Cullen, V., Kahn, I., Krastins, B., Outeiro, T. F., Pepivani, I., Ng, J., Schulz-Schaeffer, W., Kretzschmar, H. A., McLean, P. J., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.06.004 · Cited by 382 · see citing works
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Research works printed but not linked: 17
- [1]Spillantini MG, Divane A, Goedert M. Assignment of human alpha‐synuclein (SNCA) and beta‐synuclein (SNCB) geners to chromosome 4q21 and 5q35. Genomics 1995; 27: 379– 381. 7558013
- [2]Goedert M, Spillantini MG, Del Tredici K, et al. 100 years of lewy pathology. Nat Rev Neurol 2013; 9: 13– 24. 23183883
- [3]Martf MJ, Tolsa E, Campdelacreu J. Clinical overview of the synucleinopathies. Mov Disord 2003; 18: S21– S27. 14502652
- [5]Williams SM, Schult P, Sierks MR. Oligomeric a‐synuclein an B‐amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases. Eur J Neurosci 2016; 43(1): 3– 16. 26332448 PMC4718789
- [6]Shi M, Bradner J, Hancock AM. Cerebrospinal fluid biomarkers for Parkinson's disease diagnosis and progression. Ann Neurol 2011; 69: 570– 580. 21400565 PMC3117674
- [7]Ohrfelt A, Grognet P, Andreasen N, et al. Cerebrospinal fluid alpha‐synuclein in neurodegenerative disorders‐ a marker of synapse loss? Neurosci Lett 2009; 450: 332– 335. 19022350
- [8]Hong Z, Shi M, Chung KA, et al. DJ‐1 and alpha‐synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 2010; 133: 713– 726. 20157014 PMC2842513
- [9]Kruse N, Persson S, Alcolea D, et al. Validation of a quantitative cerebrospinal fluid alpha‐synuclein assay in a European‐wide interlaboratory study. Neurobiol Aging 2015; 36: 2587– 2596. 26093515
- [10]Bernis ME, Babila JT, Breid S, et al. Prion‐lie propagation of human brain‐derived alpha‐synuclein in transgenic mice expressing human wild‐type alpha‐synuclein. Acta Neuropathol Commun 2015; 3: 1– 18. 26612754 PMC4660655
- [11]Brandel JP, Corbille AG, Derkinderen P, et al. Is Parkinson's disease a prion disease? Rev Neurol (Paris) 2015; 171: 812– 824. 26563663 PMC7111738
- [12]McGuire L, Peden A, Orru C, et al. Prion seeding activity in cerebrospinal fluid from patients with sporadic Creutzfeldt‐Jakob disease patients using real‐time QuIC analysis: a potential new clinical diagnostic test with high sensitivity and specificity. Ann Neurol 2012; 72: 278– 285. 22926858 PMC3458796
- [13]Clarke R, Smith AD, Jobst KA, et al. Folate, vitamin B12 and serum total homocysteine levels n confirmed Alzheimer's disease. Arch Neurol 1998; 55: 1449– 1455. 9823829
- [14]Szewwczyk‐Krolikowski K, Tomlinson P, Nithi K, et al. The influence of age and gender on motor and non‐motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort. Parkinsonism Relat Disord 2014; 20: 99– 105. 24183678
- [15]Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease ‐ a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181– 184. 1564476 PMC1014720
- [16]Rolinski M, Zokaei N, Baig F, et al. Visual short‐term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease. Brain 2016; 139: 47– 53. 26582557 PMC4949392
- [17]Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post‐mortem pathology in idiopathic rapid‐eye‐movement sleep behaviour disorder: an observational cohort study. Lancet 2013; 12: 443– 453. 23562390
- [19]Kovacs GG, Alafuzoff I, AI‐Sarraj S, et al. Mixed brain pathologies in dementia: the BrainNet Europe consortium experience. Dement Geriatr Cogn Disord 2008; 26: 343– 350. 18849605
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- Authors
- Fairfoul, G., McGuire, L. I., Pal, S., Ironside, J. W., Neumann, J., Christie, S., Joachim, C., Esiri, M., Evetts, S. G., Rolinski, M., Baig, F., Ruffmann, C., Wade‐Martins, R., Hu, M. T. M., Parkkinen, L., & Green, A. J. E.
- Affiliations
- Western General Hospital (GB)
- John Radcliffe Hospital (GB)
- University of Oxford (GB)
- Corresponding author
- Green, Alison J. E.
- ORCID
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2016-08-28
- Volume
- 3
- Issue
- 10
- Pages
- 812-818
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC5048391
- OpenAlex
- W2513452411
- Cited by
- 608
- References
- 2
- Citations by year
- 2026: 63 · 2025: 83 · 2024: 80 · 2023: 76 · 2022: 60 · 2021: 77 · 2020: 63 · 2019: 48 · 2018: 38 · 2017: 18 · 2016: 2
- FWCI
- 26.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Explore Bristol Research (acceptedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Funders
- Michael J. Fox Foundation for Parkinson's Research (R43828)
- Department of Health
- Scottish Office Home and Health Department (R43401)
- Medical Research Council (G1000681)
- National Institute for Health Research
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- alpha-synuclein, RT-QuIC, quaking-induced conversion, cerebrospinal fluid, alpha-synuclein aggregation, dementia with Lewy bodies, Parkinson's disease, synucleinopathies, tauopathy, progressive supranuclear palsy, corticobasal degeneration, early diagnosis
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