Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease

Alzheimers Dement. 2019 May;15(5):655-665. doi: 10.1016/j.jalz.2018.12.019. Epub 2019 Mar 4.


Introduction: Four less well-studied but promising "emerging" cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40).

Methods: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations.

Results: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15-19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset.

Discussion: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.

Keywords: Alzheimer's disease; Autosomal-dominant Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Dementia; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Disease Progression*
  • Female
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neurocalcin / cerebrospinal fluid
  • Neurogranin / cerebrospinal fluid
  • Positron-Emission Tomography
  • Synaptosomal-Associated Protein 25 / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • Chitinase-3-Like Protein 1
  • Neurocalcin
  • SNAP25 protein, human
  • Synaptosomal-Associated Protein 25
  • Neurogranin