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, Regis Bordet, Magda Tsolaki, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleo, Peter Johannsen, Yvonne Freund-Levi, Lutz FroelichRik 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 journalArticleAcademicpeer-review

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Abstract

Introduction: We investigated relations between amyloid-beta (A beta) status, apolipoprotein E (APOE) e4, 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 A beta status (Ab beta- vs. A beta+), clinical diagnosis APOE epsilon 4 carriership, baseline cognition, and change in cognition.

Results: Ng and T-tau distinguished between A beta+ from A beta- individuals in each clinical group, whereas NFL and YKL-40 were associated with A beta+ in nondemented individuals only. APOE epsilon 4 carriership did not influence NFL, Ng, and YKL-40 in A beta+ individuals. NFL was the best predictor of cognitive decline in A beta+ 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. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

Keywords

  • Alzheimer's disease
  • Amyloid-beta
  • Neurofilament light
  • Neurogranin
  • YKL-40
  • Cognition
  • Cerebrospinal fluid
  • APOE
  • MILD COGNITIVE IMPAIRMENT
  • NEUROFILAMENT LIGHT
  • NEUROGRANIN
  • PROTEIN
  • PATHOLOGY
  • TAU
  • DEGENERATION
  • ASSOCIATION
  • GUIDELINES

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