title: Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer's disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Mansilla
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Rami
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Lladó
authors.affiliation: Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Iranzo
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Olives
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Mircea
authors.initials: M
authors.lastname: Balasa
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid*; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D062706:Prodromal Symptoms; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D054392:Adipokines; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; YKL-40; amyloid-$\beta_{42}$; cerebrospinal fluid; correlation; neuropsychological tests; preclinical; tau protein