title: Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer's disease.
abstract: BACKGROUND
  We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL-40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II).
  
  
  METHODS
  YKL-40 was compared among HCs (n = 21), mild cognitive impairment (n = 41), AD (n = 35), and FTD (n = 9) (level I) and among HCs (n = 21), AD pathophysiology (tau and amyloid β) negative (n = 15), tau positive (n = 15), amyloid β positive (n = 13), AD pathophysiology positive (n = 33), and FTD (n = 9) (level II).
  
  
  RESULTS
  Level I: YKL-40 discriminated AD from HC and FTD (area under the receiver operating characteristic curves [AUROCs] = 0.69, 0.71). Level II: YKL-40 discriminated tau-positive individuals and AD pathophysiology-positive individuals from HC, AD pathophysiology-positive patients from FTD (AUROCs = 0.76, 0.72, 0.73).
  
  
  CONCLUSIONS
  YKL-40 demonstrates fair performance in distinguishing tau-positive patients from HCs, suggesting it may aid clinical diagnosis and support a biomarker-guided pathophysiological stratification.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 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: Faculty of Medicine, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Toschi
authors.affiliation: 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; AXA Research Fund & UPMC Chair, Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock and DZNE, Rostock, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kilimann
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock and DZNE, Rostock, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: 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; AXA Research Fund & UPMC Chair, Paris, France; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Cavedo
authors.affiliation: 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: Antonio Melo
authors.initials: AM
authors.lastname: Dos Santos
authors.affiliation: 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: Stéphane
authors.initials: S
authors.lastname: Epelbaum
authors.affiliation: AP-HP, UF Biochimie des Maladies Neuro-métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Foudil
authors.initials: F
authors.lastname: Lamari
authors.affiliation: 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: Bruno
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Faculty of Medicine, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Floris
authors.affiliation: Faculty of Medicine, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Casa di Cura "San Raffaele Cassino", Cassino, Frosinone, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Garaci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.affiliation: 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; AXA Research Fund & UPMC Chair, Paris, France. Electronic address: harald.hampel@med.uni-muenchen.de.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1 / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003430:Cross-Sectional Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1
keywords: Alzheimer's disease; Biomarker-based diagnosis; Biomarkers; Cerebrospinal fluid; Clinical diagnosis; Dementia; Diagnostic biomarkers; Frontotemporal dementia; Mild cognitive impairment; Neurodegeneration; Neuroinflammation; YKL-40