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

Research output: Contribution to journalArticle


title = "Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease",
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.",
keywords = "Alzheimer disease, amyloid positron emission tomography, cerebrospinal fluid biomarkers, plasma biomarkers",
author = "Sebastian Palmqvist and Insel, {Philip S.} and Erik Stomrud and Shorena Janelidze and Henrik Zetterberg and Britta Brix and Udo Eichenlaub and Dage, {Jeffrey L.} and Xiyun Chai and Kaj Blennow and Niklas Mattsson and Oskar Hansson",
year = "2019",
month = dec,
day = "1",
doi = "10.15252/emmm.201911170",
language = "English",
volume = "11",
journal = "EMBO Molecular Medicine",
issn = "1757-4684",
publisher = "Federation of European Neuroscience Societies and Blackwell Publishing Ltd",
number = "12",