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, R. gis 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

Research output: Contribution to journalArticleAcademicpeer-review

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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
Issue number5
Publication statusPublished - 1 May 2019


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

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