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

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Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease. / Palmqvist, Sebastian; Insel, Philip S.; Stomrud, Erik; Janelidze, Shorena; Zetterberg, Henrik; Brix, Britta; Eichenlaub, Udo; Dage, Jeffrey L.; Chai, Xiyun; Blennow, Kaj; Mattsson, Niklas; Hansson, Oskar.

In: EMBO Molecular Medicine, Vol. 11, No. 12, e11170, 01.12.2019.

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TY - JOUR

T1 - Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

AU - Palmqvist, Sebastian

AU - Insel, Philip S.

AU - Stomrud, Erik

AU - Janelidze, Shorena

AU - Zetterberg, Henrik

AU - Brix, Britta

AU - Eichenlaub, Udo

AU - Dage, Jeffrey L.

AU - Chai, Xiyun

AU - Blennow, Kaj

AU - Mattsson, Niklas

AU - Hansson, Oskar

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

KW - Alzheimer disease

KW - amyloid positron emission tomography

KW - cerebrospinal fluid biomarkers

KW - plasma biomarkers

UR - http://www.scopus.com/inward/record.url?scp=85074814974&partnerID=8YFLogxK

U2 - 10.15252/emmm.201911170

DO - 10.15252/emmm.201911170

M3 - Article

C2 - 31709776

AN - SCOPUS:85074814974

VL - 11

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4684

IS - 12

M1 - e11170

ER -