Diagnostic Value of Cerebrospinal Fluid Biomarkers (Phospho-Tau₁₈₁, total-Tau, Aβ₄₂, and Aβ₄₀) in Prodromal Stage of Alzheimer’s Disease and Dementia with Lewy Bodies

Article type: Research Article

Authors: Bousiges, Olivier^{a; b; *} | Cretin, Benjamin^{c; d; e} | Lavaux, Thomas^a | Philippi, Nathalie^{c; d; e; f} | Jung, Barbara^{c; d; e; f} | Hezard, Sylvie^a | Heitz, Camille^{c; d; e} | Demuynck, Catherine^{c; d; e; f} | Gabel, Aurelia^a | Martin-Hunyadi, Catherine^{e; f} | Blanc, Frédéric^{c; d; e; f}

Affiliations: [a] University Hospital of Strasbourg, Laboratory of Biochemistry and Molecular Biology, Strasbourg, France | [b] University of Strasbourg and CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, Strasbourg, France | [c] University Hospital of Strasbourg, Neuropsychology Unit, Neurology Service, Strasbourg, France | [d] University of Strasbourg and CNRS, ICube laboratory UMR 7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), team IMIS/Neurocrypto, Strasbourg, France | [e] University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Strasbourg, France | [f] University Hospital of Strasbourg, Geriatrics Day Hospital, Geriatrics Service, Strasbourg, France

Correspondence: [*] Correspondence to: Olivier Bousiges, University Hospital of Strasbourg, Laboratory of Biochemistry and Molecular Biology, 67000 Strasbourg, France. Tel.: +33 368 85 19 31; Fax: +33 368 85 19 58; E-mail: [email protected].

Abstract: Background:Dementia with Lewy bodies (DLB) symptoms are close to those of Alzheimer’s disease (AD), and the differential diagnosis is difficult especially early in the disease. Unfortunately, AD biomarkers in cerebrospinal fluid (CSF), and more particularly Aβ1 - 42, appear to be altered in dementia with Lewy bodies (DLB). However, the level of these biomarkers has never been studied in the prodromal stage of the disease. Objective:To compare these biomarkers between DLB and AD, with a particular focus on the prodromal stage. Methods:A total of 166 CSF samples were collected at the memory clinic of Strasbourg. They were obtained from prodromal DLB (pro-DLB), DLB dementia, prodromal AD (pro-AD), and AD dementia patients, and elderly controls. Phospho-Tau181, total-Tau, Aβ42, and Aβ40 were measured in the CSF. Results:At the prodromal stage, contrary to AD patients, DLB patients’ biomarker levels in the CSF were not altered. At the demented stage of DLB, Aβ42 levels were reduced as well as Aβ40 levels. Thus, the Aβ42/Aβ40 ratio remained unchanged between the prodromal and demented stages, contrary to what was observed in AD. Tau and Phospho-Tau181 levels were unaltered in DLB patients. Conclusions:We have shown that at the prodromal stage the DLB patients had no pathological profile. Consequently, CSF AD biomarkers are extremely useful for differentiating AD from DLB patients particularly at this stage when the clinical diagnosis is difficult. Thus, these results open up new perspectives on the interpretation of AD biomarkers in DLB.

Keywords: Aβ₄₂, Aβ₄₀, Aβ₄₂/Aβ₄₀ ratio, Alzheimer’s disease, cerebrospinal fluid biomarkers, dementia with Lewy bodies, dementia, phospho-Tau181, prodromal, total-Tau

DOI: 10.3233/JAD-150731

Journal: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1069-1083, 2016