Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

Failures in Alzheimer's disease (AD) drug trials highlight the need to further explore disease mechanisms and alterations of biomarkers during the development of AD. Using cross-sectional data from 377 participants in the BioFINDER study, we examined seven cerebrospinal fluid (CSF) and six plasma biomarkers in relation to β-amyloid (Aβ) PET uptake to understand their evolution during AD. In CSF, Aβ42 changed first, closely followed by Aβ42/Aβ40, phosphorylated-tau (P-tau), and total-tau (T-tau). CSF neurogranin, YKL-40, and neurofilament light increased after the point of Aβ PET positivity. The findings were replicated using Aβ42, Aβ40, P-tau, and T-tau assays from five different manufacturers. Changes were seen approximately simultaneously for CSF and plasma biomarkers. Overall, plasma biomarkers had smaller dynamic ranges, except for CSF and plasma P-tau which were similar. In conclusion, using state-of-the-art biomarkers, we identified the first changes in Aβ, closely followed by soluble tau. Only after Aβ PET became abnormal, biomarkers of neuroinflammation, synaptic dysfunction, and neurodegeneration were altered. These findings lend in vivo support of the amyloid cascade hypotheses in humans.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • University of California, San Francisco
  • Sahlgrenska Academy
  • Sahlgrenska University Hospital
  • University College London
  • Roche Diagnostics
  • Lilly Research Laboratories
  • UK Dementia Research Institute
  • Euroimmun Medizinische Labordiagnostika AG
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Alzheimer disease, amyloid positron emission tomography, cerebrospinal fluid biomarkers, plasma biomarkers
Original languageEnglish
Article numbere11170
JournalEMBO Molecular Medicine
Volume11
Issue number12
Publication statusPublished - 2019 Dec 1
Publication categoryResearch
Peer-reviewedYes