Decreased sAβPPβ, Aβ₃₈, and Aβ₄₀ Cerebrospinal Fluid Levels in Frontotemporal Dementia

Article type: Research Article

Authors: Gabelle, Audrey^{a; b; c; *} | Roche, Stéphane^{d; 1} | Gény, Christian^a | Bennys, Karim^a | Labauge, Pierre^e | Tholance, Yannick^{f; j} | Quadrio, Isabelle^{f; j} | Tiers, Laurent^d | Gor, Baptiste^d | Boulanghien, Justine^d | Chaulet, Chloé^a | Vighetto, Alain^{g; j} | Croisile, Bernard^{h; j} | Krolak-Salmon, Pierre^{i; j} | Perret-Liaudet, Armand^{f; j; k} | Touchon, Jacques^{a; b} | Lehmann, Sylvain^{b; c; d}

Affiliations: [a] Centre Mémoire Ressources Recherche Montpellier, Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Montpellier cedex 5, France | [b] Université Montpellier 1, Faculté de Médecine, Montpellier, France | [c] UPR 11₄₂, CNRS, Institut de Génétique Humaine, Montpellier Cedex 5, France | [d] Laboratoire de Biochimie Protéomique Clinique et CCBHM, Institut de Recherche en Biothérapie, Centre Hospitalier Universitaire Saint Eloi, Montpellier Cedex 5, France | [e] Service de Neurologie, Centre Hospitalier Universitaire de Nîmes, Hôpital Caremeau, Place du Professeur Robert Debré, Nîmes Cedex 9, France | [f] Service de Neurobiologie, Biochimie et Biologie moléculaire, Groupement Hospitalier Est, Hospices Civils de Lyon / Université Claude Bernard Lyon 1, Bron cedex, France | [g] Service de Neurologie; Unité 402, Groupement Hospitalier Est, Hospices Civils de Lyon / Université Claude Bernard Lyon 1, Bron cedex, France | [h] Service de Neuropsychologie; Groupement Hospitalier Est, Hospices Civils de Lyon / Université Claude Bernard Lyon 1, Bron cedex, France | [i] Médecine Gériatrique, Hôpital des Charpennes, 27, Hospices Civils de Lyon, Villeurbanne, France | [j] Centre Mémoire Ressources Recherche de Lyon, Hospices Civils de Lyon, 3 quai des Célestins, Lyon, France | [k] Centre de Recherche en Neurosciences de Lyon (équipe 11 BioRaN) Université Lyon 1, Bron cedex, France

Correspondence: [*] Correspondence to: Prof. Sylvain Lehmann, Laboratoire de Biochimie Protéomique Clinique, Institut de Recherche en Biothérapie, Centre Hospitalier Universitaire Saint Eloi, 80 Avenue Augustin Fliche, 3₄₂95 Montpellier Cedex 5, France. E-mail: s-lehmann@chu-montpellier.fr and Dr. Audrey Gabelle, Department of Neurology, Montpellier University Hospital, CHU Gui de Chauliac, 80 Avenue Augustin Fliche, 3₄₂95 Montpellier Cedex 5, France. Tel.: +33 4 67 33 60 29; Fax: +33 4 67 63 16 28; E-mail: s-lehmann@chu-montpellier.fr and Dr. Audrey Gabelle, Department of Neurology, Montpellier University Hospital, CHU Gui de Chauliac, 80 Avenue Augustin Fliche, 3₄₂95 Montpellier Cedex 5, France. Tel.: +33 4 67 33 60 29; Fax: +33 4 67 63 16 28; E-mail: a-gabelle@chu-montpellier.fr and audreygabelle@hotmail.com.

Note: [1] Present address: Laboratoire “Génétique Médicale et Génomique Fonctionnelle”, Faculté de Médecine de la Timone, 27, Bd Jean Moulin, 13385 Marseille Cedex 05, France.

Abstract: To improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia.

Keywords: Alzheimer's disease, frontotemporal dementia, CSF biomarkers, CSF amyloid peptides, Aβ₃₈

DOI: 10.3233/JAD-2011-110515

Journal: Journal of Alzheimer's Disease, vol. 26, no. 3, pp. 553-563, 2011