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. 2020 Sep 29;12(1):120.
doi: 10.1186/s13195-020-00684-5.

Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

Olivier Bousiges  1   2   3   4 , Nathalie Philippi  5   6 , Thomas Lavaux  7 , Armand Perret-Liaudet  8   9   10 , Ingolf Lachmann  11 , Caroline Schaeffer-Agalède  7 , Pierre Anthony  12 , Anne Botzung  5 , Lucie Rauch  5 , Barbara Jung  5 , Paulo Loureiro de Sousa  6 , Catherine Demuynck  5 , Catherine Martin-Hunyadi  5 , Benjamin Cretin  5   6 , Frédéric Blanc  5   6
Affiliations

Differential diagnostic value of total alpha-synuclein assay in the cerebrospinal fluid between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

Olivier Bousiges et al. Alzheimers Res Ther. .

Abstract

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.

Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured.

Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB.

Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer's biomarker does not improve the differential diagnosis between AD and DLB.

Trial registration: ClinicalTrials.gov, NCT01876459 (AlphaLewyMa).

Keywords: Alzheimer’s disease; Cerebrospinal fluid biomarkers; Dementia; Dementia with Lewy bodies; Prodromal; Total alpha-synuclein.

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Conflict of interest statement

Ingolf Lachmann provided the ELISA alpha-synuclein kits and reports that he is an employee of AJ Roboscreen GmbH®, Leipzig, Germany.

Figures

Fig. 1
Fig. 1
Flowchart of patient selection from AlphaLewyMA study. Center 1: CHU de Hautepierre; center 2: Hôpital de la Robertsau; center 3: Hôpitaux Civils de Colmar; AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; Pro-AD, prodromal AD; Pro-DLB, prodromal DLB; AD-d, AD demented; DLB-d, DLB demented
Fig. 2
Fig. 2
Total alpha-synuclein assay discriminates between AD and DLB (a) and b scatterplots of CSF alpha-synuclein. a CSF concentrations of total alpha-synuclein in each patient group (the number of patients per group was as follows: CS n = 21, pro-DLB n = 51, DLB-d n = 16, pro-AD n = 33, AD-d n = 32, and AD/DLB-d n = 11) and b CSF concentration of alpha-synuclein in CS, DLB (pro-DLB + DLB-d), AD (pro-AD + AD-d), and AD/DLB (mixed pathologies: pro-AD/DLB + AD/DLB-d). ***P < 0.001; *P < 0.05. P values were calculated using the Kruskal-Wallis test with Dunn’s multiple comparison test. c Alpha-synuclein ROC curve between DLB and AD groups. Prodromal and demented patients were pooled in each group. Number of patients per group: DLB n = 67, AD n = 65. Se, sensitivity; Sp, specificity
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