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

Isabelle Bos*, Stephanie Vos, Frans Verhey, Philip Scheltens, Charlotte Teunissen, Sebastiaan Engelborghs, Kristel Sleegers, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Régis Bordet, Magda Tsolaki, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleó, Peter Johannsen, Yvonne Freund-Levi, Lutz FrölichRik Vandenberghe, Sarah Westwood, Valerija Dobricic, Frederik Barkhof, Cristina Legido-Quigley, Lars Bertram, Simon Lovestone, Johannes Streffer, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Pieter Jelle Visser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)644-654
Number of pages11
JournalAlzheimer's and Dementia
Volume15
Issue number5
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • APOE
  • Cerebrospinal fluid
  • Cognition
  • Neurofilament light
  • Neurogranin
  • YKL-40

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