Additional Use of Aβ₄₂/Aβ₄₀ Ratio with Cerebrospinal Fluid Biomarkers P-Tau and Aβ₄₂ Increases the Level of Evidence of Alzheimer's Disease Pathophysiological Process in Routine Practice

Article type: Research Article

Authors: Sauvée, Mathilde^b | DidierLaurent, Guerric^a | Latarche, Clotilde^{c; d} | Escanyé, Marie-Christine^a | Olivier, Jean-Luc^{a; e} | Malaplate-Armand, Catherine^{a; e; *}

Affiliations: [a] Laboratoire de Biochimie et Biologie Moléculaire, UF Oncologie – Endocrinologie – Neurobiologie, Hôpital Central, Centre Hospitalier Universitaire, Nancy, France | [b] Service de Neurologie, Centre Hospitalier Universitaire, Nancy, France | [c] INSERM, CIC-EC, CIE6, Université de Lorraine, Nancy, France | [d] Epidémiologie et Evaluation Cliniques, Centre Hospitalier Universitaire, Nancy, France | [e] UR AFPA – USC 340, Equipe BFLA, Université de Lorraine, Nancy, France

Correspondence: [*] Correspondence to: Dr. Catherine Malaplate-Armand, Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny – CO n° 34 – 54035 Nancy Cedex, France. Tel.: +33 3 83 85 27 85; Fax: +33 3 83 85 19 69; E-mail: [email protected].

Abstract: Background:Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer’s disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-β (Aβ)42 alone can be observed. In these cases, Aβ42/Aβ40 ratio could be more relevant than Aβ42 absolute values by considering inter-individual variations in the total amyloid load. Objective:The objective of this study was to assess the use of Aβ42/Aβ40 ratio to improve the accuracy of biological conclusions in the diagnosis of patients with ambiguous CSF Aβ42 or tau results. Methods:Among 386 lumbar punctures analyzed in the lab in 2 years, 122 showed ambiguous biological data that were completed by CSF Aβ40 quantification and Aβ42/Aβ40 ratio calculation. A biological conclusion was then made using 0.05 as the Aβ42/Aβ40 ratio cut-off. Results:Our results showed that one-third of the biological profiles of patients with atypical dementia were ambiguous. The addition of Aβ42/Aβ40 ratio increased the proportion of interpretable biological profiles from 69% to 87%, without changing the conclusion when usual biomarkers (Aβ42 and P-tau) were concordant. Conclusion:Our results support the use of the Aβ42/Aβ40 ratio in addition to the usual CSF AD biomarkers for patients with ambiguous biological profiles. This method could be specifically directed to this population in order to improve the level of certainty for clinical routine practice.

Keywords: Aβ₄₀ peptide, Aβ₄₀/Aβ₄₂ ratio, Aβ₄₂ peptide, Alzheimer's disease, cerebrospinal fluid, diagnosis, differential diagnosis, P-tau

DOI: 10.3233/JAD-131838

Journal: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 377-386, 2014