Cerebrospinal Fluid Level of YKL-40 Protein in Preclinical and Prodromal Alzheimer's Disease

Article type: Research Article

Authors: Antonell, Anna^a | Mansilla, Alicia^a | Rami, Lorena^a | Lladó, Albert^a | Iranzo, Alex^b | Olives, Jaume^a | Balasa, Mircea^a | Sánchez-Valle, Raquel^a | Molinuevo, José Luis^{a; *}

Affiliations: [a] Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain | [b] Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain

Correspondence: [*] Correspondence to: José Luis Molinuevo, MD, PhD, Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, C/Villarroel, 170, 08036 Barcelona, Spain. Tel.: +34 93 227 57 85; Fax: +34 93 227 57 83; E-mail: [email protected].

Abstract: Background:An increase in YKL-40 levels seems to correlate with disease severity and poor prognosis in many diseases, including several neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease (AD). Specifically, YKL-40 protein is increased in mild AD with respect to controls, both in cerebrospinal fluid (CSF) and plasma. Objective:We hypothesize that subjects in the preclinical (Pre-AD) and prodromal (Prod-AD) stage of AD could already present an increase in CSF YKL-40 levels with respect to healthy controls and idiopathic REM sleep behavior disorder (iRBD) subjects, included as a control group of a distinct neurological disease. Methods:We measured CSF YKL-40 levels using a commercial ELISA kit in a cohort of 95 subjects, consisting of controls (n = 43), Pre-AD (n = 18), Prod-AD (n = 22), and iRBD (n = 12) subjects. We explored for possible correlations of YKL-40 levels with demographic characteristics, a wide battery of neuropsychological tests, and the AD CSF biomarkers: amyloid-β42 (Aβ42), total-tau protein (t-tau), and phosphorylated-tau protein (p-tau). Results:We detected statistically significant differences between Prod-AD patients and controls. YKL-40 levels showed a significant correlation with t-tau and p-tau levels in the predementia AD continuum and the Pre-AD group. We also observed significant correlations with the MMSE, FCSRT, and M@T tests within the AD continuum, but not in iRBD subjects. Conclusion:Our data suggest that CSF YKL-40 levels, although not useful as a diagnostic marker for Prod-AD, may be a valuable marker to detect early physiopathological changes potentially linked with the neurodegenerative process.

Keywords: Alzheimer's disease, amyloid-β₄₂, cerebrospinal fluid, correlation, neuropsychological tests, preclinical, tau protein, YKL-40

DOI: 10.3233/JAD-140624

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 901-908, 2014