Total alpha-synuclein assay in cerebrospinal fluid is of interest in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

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. Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Furthermore, alpha-synuclein levels were elevated not only in AD patients with a typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also in AD patients with an atypical “Alzheimer” profile (i.e. one or no pathological biomarkers).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarkers.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)