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

Palmqvist, Sebastian LU orcid ; Insel, Philip S. LU ; Stomrud, Erik LU orcid ; Janelidze, Shorena LU ; Zetterberg, Henrik LU ; Brix, Britta ; Eichenlaub, Udo ; Dage, Jeffrey L. ; Chai, Xiyun and Blennow, Kaj LU , et al. (2019) In EMBO Molecular Medicine 11(12).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer disease, amyloid positron emission tomography, cerebrospinal fluid biomarkers, plasma biomarkers
in
EMBO Molecular Medicine
volume
11
issue
12
article number
e11170
publisher
Wiley-Blackwell
external identifiers
  • scopus:85074814974
  • pmid:31709776
ISSN
1757-4676
DOI
10.15252/emmm.201911170
language
English
LU publication?
yes
id
ce8c64de-b913-4e3d-a46b-0a44342716ea
date added to LUP
2019-12-11 16:28:41
date last changed
2024-04-17 01:30:38
@article{ce8c64de-b913-4e3d-a46b-0a44342716ea,
  abstract     = {{<p>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.</p>}},
  author       = {{Palmqvist, Sebastian and Insel, Philip S. and Stomrud, Erik and Janelidze, Shorena and Zetterberg, Henrik and Brix, Britta and Eichenlaub, Udo and Dage, Jeffrey L. and Chai, Xiyun and Blennow, Kaj and Mattsson, Niklas and Hansson, Oskar}},
  issn         = {{1757-4676}},
  keywords     = {{Alzheimer disease; amyloid positron emission tomography; cerebrospinal fluid biomarkers; plasma biomarkers}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.15252/emmm.201911170}},
  doi          = {{10.15252/emmm.201911170}},
  volume       = {{11}},
  year         = {{2019}},
}