Endostatin Level in Cerebrospinal Fluid of Patients with Alzheimer's Disease

Article type: Research Article

Authors: Salza, Romain^a | Oudart, Jean-Baptiste^{b; c} | Ramont, Laurent^{b; c} | Maquart, François-Xavier^{b; c} | Bakchine, Serge^d | Thoannès, Henri^b | Ricard-Blum, Sylvie^{a; *}

Affiliations: [a] Bases Moléculaires et Structurales des Systèmes Infectieux, UMR 5086 CNRS, Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France | [b] CHU de Reims, Laboratoire Central de Biochimie, Reims, France | [c] Université de Reims Champagne-Ardenne, CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, Reims, France | [d] CHU de Reims, Service de Neurologie, Centre Mémoire de Ressources et de Recherche Champagne-Ardenne (CMRR), Reims, France

Correspondence: [*] Correspondence to: Professor Sylvie Ricard-Blum, UMR 5086 CNRS, Université Lyon 1(BMSSI), 7 passage du Vercors, 69367 Lyon cedex 07, France. Tel.: +33 4 37 65 29 26; Fax: +33 4 72 72 26 04; E-mail: [email protected].

Abstract: The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (−49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (−21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD.

Keywords: Alzheimer's disease, amyloid-β_1-42 peptide, biomarkers, cerebrospinal fluid, endostatin, hyperphosphorylated tau, neurodegenerative diseases, tau

DOI: 10.3233/JAD-142544

Journal: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1253-1261, 2015