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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • 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
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Artikelnummere11170
TidskriftEMBO Molecular Medicine
Volym11
Utgåva nummer12
StatusPublished - 2019 dec 1
PublikationskategoriForskning
Peer review utfördJa