Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease

Dominantly Inherited Alzheimer Network

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)655-665
Number of pages11
JournalAlzheimer's and Dementia
Volume15
Issue number5
DOIs
StatePublished - May 2019

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Keywords

  • Alzheimer's disease
  • Autosomal-dominant Alzheimer's disease
  • Biomarkers
  • Cerebrospinal fluid
  • Dementia
  • Neuroinflammation

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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