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Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson's disease and degenerative dementias

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  • Relevant conflicts of interest/financial disclosures: The laboratory of Omar M. El-Agnaf is supported by the Michael J. Fox Foundation for Parkinson's Research (New York). Full financial disclosures and author roles may be found in the online version of this article.

  • Part of this work was supported by EU Grants cNEUPRO (contract no. 199 LSHM-CT-2007-037950) and Progetti Finalizzati e Strategici Ministero della Salute 2006/2007 (to A.R. and P.C.).

Abstract

Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, Aβ1–42, total tau, phosphorylated tau, and α-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. Aβ1–42, total tau, phosphorylated tau, and α-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean α-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of α-synuclein with total tau (r = −0.196, P < .01) was observed. In the group of patients with Parkinson's disease, Aβ1–42, total tau, and phosphorylated tau values were similar to controls, whereas total tau/α-synuclein and phosphorylated tau/α-synuclein ratios showed the lowest values. Cerebrospinal fluid α-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/α-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of α-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/α-synuclein and phosphorylated tau/α-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society

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