title: Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer's disease.
abstract: BACKGROUND
  Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer's disease (AD). Neurogranin and YKL-40 in cerebrospinal fluid (CSF) are newly discovered markers indicating synaptic damage and microglial activation, respectively.
  
  
  METHODS
  CSF samples from 95 individuals including 39 patients with AD dementia (AD-D), 13 with mild cognitive impairment (MCI) due to AD (MCI-AD), 29 with MCI not due to AD (MCI-o) and 14 patients with non-AD dementias (non-AD-D) were analyzed for neurogranin and YKL-40.
  
  
  RESULTS
  Patients with dementia or MCI due to AD showed elevated levels of CSF neurogranin (p < 0.001 for AD-D and p < 0.05 for MCI-AD) and YKL-40 (p < 0.05 for AD-D and p = 0.15 for MCI-AD) compared to mildly cognitively impaired subjects not diagnosed with AD. CSF levels of neurogranin and YKL-40 did not differ between MCI not due to AD and non-AD dementias. In AD subjects no correlation between YKL-40 and neurogranin was found. The CSF neurogranin levels correlated moderately with tau and p-tau but not with Aβ42 or the MMSE in AD samples. No relevant associations between YKL-40 and MMSE or the core AD biomarkers, Aβ42, t-tau and p-tau were found in AD subjects.
  
  
  CONCLUSIONS
  Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core AD biomarkers, reflecting additional pathological changes in the course of AD.
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. konstantin.hellwig@uk-erlangen.de.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Hellwig
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. hlin.johansson-schmidt@neuro.gu.se.|AlzeCure Foundation, Karolinska Institutet Science Park, Huddinge, Sweden. hlin.johansson-schmidt@neuro.gu.se.
authors.forename: Hlin
authors.initials: H
authors.lastname: Kvartsberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. erik.portelius@neuro.gu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. ulf.andreasson@neuro.gu.se.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. timo.oberstein@uk-erlangen.de.
authors.forename: Timo Jan
authors.initials: TJ
authors.lastname: Oberstein
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. piotr.lewczuk@uk-erlangen.de.|Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland. piotr.lewczuk@uk-erlangen.de.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. kaj.blennow@neuro.gu.se.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. johannes.kornhuber@uk-erlangen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. manuel.maler@uk-erlangen.de.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Maler
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. henrik.zetterberg@clinchem.gu.se.|Department of Molecular Neuroscience, UCL Institute of Neurology, London, WC1N 3BG, UK. henrik.zetterberg@clinchem.gu.se.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry and Psychotherapy, University clinic Erlangen and Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany. philipp.spitzer@uk-erlangen.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Spitzer
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid* / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D018450:Disease Progression; D005260:Female; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051579:Neurogranin / Q000134:cerebrospinal fluid* / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D054392:Adipokines; D016229:Amyloid beta-Peptides; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D016875:tau Proteins; D051579:Neurogranin