title: Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease.
abstract: BACKGROUND
  Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear.
  
  
  OBJECTIVE
  To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions.
  
  
  METHODS
  We measured markers of amyloid-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses: subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers.
  
  
  RESULTS
  CSF levels of sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD.
  
  
  CONCLUSIONS
  CSF biomarkers of AβPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions.
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcolea
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Carmona-Iragui
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Suárez-Calvet
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: M Belén
authors.initials: MB
authors.lastname: Sánchez-Saudinós
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sala
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Antón-Aguirre
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid*; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: C545487:APP protein, human; D054392:Adipokines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer's disease; YKL-40; amyloid-β protein precursor; biological markers; cerebrospinal fluid; frontotemporal dementia; inflammation; β-secretase