Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Alzheimers Dement. 2019 May;15(5):644-654. doi: 10.1016/j.jalz.2019.01.004. Epub 2019 Mar 8.


Introduction: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).

Methods: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.

Results: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.

Discussion: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

Keywords: APOE; Alzheimer's disease; Amyloid-β; Cerebrospinal fluid; Cognition; Neurofilament light; Neurogranin; YKL-40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / physiopathology
  • Female
  • Humans
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neurogranin / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • Neurofilament Proteins
  • tau Proteins
  • Neurogranin