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. 2019 Dec;6(12):2426-2436.
doi: 10.1002/acn3.50944. Epub 2019 Nov 19.

α-Synuclein in blood cells differentiates Parkinson's disease from healthy controls

Suaad Abd Elhadi  1 , Jessica Grigoletto  1 , Maura Poli  2 , Paolo Arosio  2 , David Arkadir  3 , Ronit Sharon  1
Affiliations

α-Synuclein in blood cells differentiates Parkinson's disease from healthy controls

Suaad Abd Elhadi et al. Ann Clin Transl Neurol. 2019 Dec.

Abstract

Objective: To determine whether blood cells expressed α-Syn can differentiate Parkinson's disease (PD) from healthy controls (HC).

Methods: The concentrations of α-Syn were determined in samples of blood cell pellets using a quantitative Lipid-ELISA assay. In addition, the levels of total protein, hemoglobin, iron and H-ferritin were determined. The study includes samples from the Biofind cohort (n = 46 PD and 45 HC) and results were validated with an additional cohort (n = 35 PD and 28 HC).

Results: A composite biomarker consisting of the concentrations of total α-Syn, proteinase-K resistant (PKres ) α-Syn and phospho-Serine 129 α-Syn (PSer 129), is designed based on the analysis of the discovery BioFIND cohort. This composite biomarker differentiates a PD subgroup, presenting motor symptoms without dementia from a HC group, with a convincing accuracy, represented by an AUC = 0.81 (95% CI, 0.71 to 0.92). Closely similar results were obtained for the validation cohort, that is, AUC = 0.81, (95% CI, 0.70 to 0.94).

Interpretation: Our results demonstrate the potential usefulness of blood cells expressed α-Syn as a biomarker for PD.

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Conflict of interest statement

Authors S.A.E., J.G., M.P., P.A. and D.A have no conflict of interests. R.S. owns patent PCT/IL2014/050191: An ELISA method for a sensitive detection of alpha synuclein, consisting of its phospholipids binding properties.

Figures

Figure 1
Figure 1
α‐Syn levels in samples of whole blood cells determined by Lipid ELISA. Graph showing mean ± SD of total α‐Syn (A), PKres α‐Syn (C) or PSer129 α‐Syn (E) detected through binding to a mixture of PI:PS:PE:GM1 (1:1:1:1) that were immobilized to the ELISA plate using methanol or cyclohexene as a solvent. Pearson’s correlation coefficient for total α‐Syn (B), PKres α‐Syn (D) and PSer129 α‐Syn (F) with total UPDRS (I + II+III) scores. HC, healthy controls; PD‐M, PD with motor symptoms; PD‐D, PD with cognitive symptoms. *P < 0.05; **P < 0.01 (Kruskal–Wallis test).
Figure 2
Figure 2
A composite biomarker differentiates PD with motor symptoms (PD‐M) and healthy controls (HC) in the BioFIND (discovery) cohort. (A) Graph showing the classification of the composite biomarker, consisting of the concentrations of total α‐Syn, PKres and PSer129 α‐Syn, combined with logistic regression as determined in HC (n = 45), PD‐M (n = 32), and PD‐D (n = 14) groups. (B) The composite biomarker in PD‐M correlates with UPDRS (I + II+III). (C) ROC curve showing the strength of the composite biomarker in differentiating the PD‐M and HC groups.
Figure 3
Figure 3
A composite biomarker differentiates PD‐M and healthy controls (HC) in the validation cohort. (A) Graph showing the classification of the composite biomarker, consisting of the concentrations of total α‐Syn, PKres and PSer129 α‐Syn, combined with logistic regression as determined in HC (n = 28) and PD‐M (n = 35). (B) Pearson’s correlation coefficient for the composite biomarker in PD‐M with UPDRS (I + II+III). (C) ROC curve showing the strength of the composite biomarker in differentiating the PD‐M and HC groups.
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