title: Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer's disease and other neurodegenerative diseases.
abstract: Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 - an indicator of microglial activation - has recently been identified by proteomic studies as a candidate biomarker for Alzheimer's disease (AD). Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia. Moreover, a positive association between CSF YKL-40 and other biomarkers of neurodegeneration - particularly total tau protein - has been reported during the asymptomatic preclinical stage of AD and other neurodegenerative diseases. Albeit preliminary, current data do not support an association between APOE-ε4 status and CSF YKL-40 concentrations. When interpreting the diagnostic/prognostic significance of CSF YKL-40 concentrations in neurodegenerative diseases, potential confounders - including age, metabolic and cardiovascular risk factors, diagnostic criteria for selecting cases/controls - need to be considered. Expert opinion/commentary: CSF YKL-40 represents a pathophysiological biomarker reflecting immune/inflammatory mechanisms in neurodegenerative diseases, associated with tau protein pathology. Besides being associated with tau pathology, CSF YKL-40 adds to the growing array of biomarkers reflecting distinct molecular brain mechanisms potentially useful for stratifying individuals for biomarker-guided, targeted anti-inflammatory therapies emerging from precision medicine.
authors.affiliation: a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.|b AXA Research Fund UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie , Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: Filippo
authors.initials: F
authors.lastname: Baldacci
authors.affiliation: b AXA Research Fund UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie , Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: b AXA Research Fund UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie , Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.|c IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli , Brescia , Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Cavedo
authors.affiliation: a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.affiliation: b AXA Research Fund UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie , Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital , Paris , France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D040901:Proteomics; D012307:Risk Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016875:tau Proteins
keywords: Alzheimer’s disease; YKL-40; biomarkers; cerebrospinal fluid; dementia; mild cognitive impairment; neurodegenerative diseases; neuroinflammation