Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer's disease

Alzheimers Res Ther. 2015 Dec 24;7:74. doi: 10.1186/s13195-015-0161-y.


Introduction: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / cerebrospinal fluid*
  • Adipokines / metabolism
  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Chitinase-3-Like Protein 1
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / diagnosis
  • Disease Progression
  • Female
  • Humans
  • Lectins / cerebrospinal fluid*
  • Lectins / metabolism
  • Male
  • Middle Aged
  • Neurogranin / cerebrospinal fluid*
  • Neurogranin / metabolism
  • tau Proteins / cerebrospinal fluid


  • Adipokines
  • Amyloid beta-Peptides
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • tau Proteins
  • Neurogranin