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Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies

Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Beca...

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Autores principales: Foulds, P.G., Yokota, O., Thurston, A., Davidson, Y., Ahmed, Z., Holton, J., Thompson, J.C., Akiyama, H., Arai, T., Hasegawa, M., Gerhard, A., Allsop, D., Mann, D.M.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657198/
https://www.ncbi.nlm.nih.gov/pubmed/21856424
http://dx.doi.org/10.1016/j.nbd.2011.08.003
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author Foulds, P.G.
Yokota, O.
Thurston, A.
Davidson, Y.
Ahmed, Z.
Holton, J.
Thompson, J.C.
Akiyama, H.
Arai, T.
Hasegawa, M.
Gerhard, A.
Allsop, D.
Mann, D.M.A.
author_facet Foulds, P.G.
Yokota, O.
Thurston, A.
Davidson, Y.
Ahmed, Z.
Holton, J.
Thompson, J.C.
Akiyama, H.
Arai, T.
Hasegawa, M.
Gerhard, A.
Allsop, D.
Mann, D.M.A.
author_sort Foulds, P.G.
collection PubMed
description Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Because PD (and the related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by the deposition of aggregated forms of α-synuclein protein (α-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of α-syn, and phosphorylated and phosphorylated oligomeric forms of α-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of α-syn were measured in post mortem samples of ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric α-syn, and phosphorylated α-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric α-syn did differ significantly (p < 0.001) amongst the different diagnostic groups. Although all 4 measures of α-syn were higher in patients with MSA compared to all other diagnostic groups, these were only significantly raised (p < 0.001) in MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms of α-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other α-synucleinopathies. However, it does not appear to be of help in distinguishing patients with PD and DLB from those with PSP or from control subjects. Western blots show that the principal form of α-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric α-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation.
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spelling pubmed-36571982013-05-18 Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies Foulds, P.G. Yokota, O. Thurston, A. Davidson, Y. Ahmed, Z. Holton, J. Thompson, J.C. Akiyama, H. Arai, T. Hasegawa, M. Gerhard, A. Allsop, D. Mann, D.M.A. Neurobiol Dis Article Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Because PD (and the related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by the deposition of aggregated forms of α-synuclein protein (α-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of α-syn, and phosphorylated and phosphorylated oligomeric forms of α-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of α-syn were measured in post mortem samples of ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric α-syn, and phosphorylated α-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric α-syn did differ significantly (p < 0.001) amongst the different diagnostic groups. Although all 4 measures of α-syn were higher in patients with MSA compared to all other diagnostic groups, these were only significantly raised (p < 0.001) in MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms of α-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other α-synucleinopathies. However, it does not appear to be of help in distinguishing patients with PD and DLB from those with PSP or from control subjects. Western blots show that the principal form of α-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric α-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation. Academic Press 2012-01 /pmc/articles/PMC3657198/ /pubmed/21856424 http://dx.doi.org/10.1016/j.nbd.2011.08.003 Text en © 2012 Elsevier Inc. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Foulds, P.G.
Yokota, O.
Thurston, A.
Davidson, Y.
Ahmed, Z.
Holton, J.
Thompson, J.C.
Akiyama, H.
Arai, T.
Hasegawa, M.
Gerhard, A.
Allsop, D.
Mann, D.M.A.
Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title_full Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title_fullStr Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title_full_unstemmed Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title_short Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies
title_sort post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, parkinson's disease and dementia with lewy bodies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657198/
https://www.ncbi.nlm.nih.gov/pubmed/21856424
http://dx.doi.org/10.1016/j.nbd.2011.08.003
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