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

NEUROBIOLOGY OF DISEASE

卷:45

Article

Foulds, P. G.¹  Yokota, O.^2,3  Thurston, A.²  Davidson, Y.²  Ahmed, Z.⁴  Holton, J.⁴  Thompson, J. C.⁵  Akiyama, H.⁶  Arai, T.⁶  Hasegawa, M.⁷  Gerhard, A.²  Allsop, D.¹  Mann, D. M. A.² 

[1] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster LA1 4AY, England

[2] Univ Manchester, Hope Hosp, Neurodegenerat & Mental Hlth Res Grp, Sch Community Based Med, Salford M6 8HD, Lancs, England

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neuropsychiat, Okayama 7008558, Japan

[4] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[5] Salford Royal Hosp NHS Fdn Trust, Hope Hosp, Cerebral Funct Unit, Salford M6 8HD, Lancs, England

[6] Tokyo Inst Psychiat, Dept Psychogeriatr, Setagaya Ku, Tokyo 1568585, Japan

[7] Tokyo Inst Psychiat, Dept Mol Neurobiol, Setagaya Ku, Tokyo 1568585, Japan

关键词: Parkinson's disease;    Dementia with Lewy Bodies;    Multiple system atrophy;    Alpha synuclein;    Cerebrospinal fluid;   

DOI  :  10.1016/j.nbd.2011.08.003

来源: Elsevier

【 摘 要 】

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 alpha-synuclein protein (alpha-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of alpha-syn, and phosphorylated and phosphorylated oligomeric forms of alpha-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of alpha-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 alpha-syn, and phosphorylated alpha-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric alpha-syn did differ significantly (p < 0.001) amongst the different diagnostic groups. Although all 4 measures of alpha-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 alpha-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other alpha-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 alpha-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric alpha-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation. (C) 2011 Elsevier Inc. All rights reserved.

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