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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-11-01
|
| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201911170 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332490979770368 |
|---|---|
| author | Sebastian Palmqvist Philip S Insel Erik Stomrud Shorena Janelidze Henrik Zetterberg Britta Brix Udo Eichenlaub Jeffrey L Dage Xiyun Chai Kaj Blennow Niklas Mattsson Oskar Hansson |
| author_facet | Sebastian Palmqvist Philip S Insel Erik Stomrud Shorena Janelidze Henrik Zetterberg Britta Brix Udo Eichenlaub Jeffrey L Dage Xiyun Chai Kaj Blennow Niklas Mattsson Oskar Hansson |
| author_sort | Sebastian Palmqvist |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d89881cae46c49b3a1cf51981d7d680a |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2019-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-d89881cae46c49b3a1cf51981d7d680a2025-08-20T03:46:11ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-11-01111211310.15252/emmm.201911170Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's diseaseSebastian Palmqvist0Philip S Insel1Erik Stomrud2Shorena Janelidze3Henrik Zetterberg4Britta Brix5Udo Eichenlaub6Jeffrey L Dage7Xiyun Chai8Kaj Blennow9Niklas Mattsson10Oskar Hansson11Clinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityClinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityClinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityClinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of GothenburgEuroimmun AGRoche Diagnostics GmbHEli Lilly and CompanyEli Lilly and CompanyDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of GothenburgClinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityClinical Memory Research Unit, Department of Clinical Sciences, Lund UniversityAbstract 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.https://doi.org/10.15252/emmm.201911170Alzheimer diseaseamyloid positron emission tomographycerebrospinal fluid biomarkersplasma biomarkers |
| spellingShingle | Sebastian Palmqvist Philip S Insel Erik Stomrud Shorena Janelidze Henrik Zetterberg Britta Brix Udo Eichenlaub Jeffrey L Dage Xiyun Chai Kaj Blennow Niklas Mattsson Oskar Hansson Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease EMBO Molecular Medicine Alzheimer disease amyloid positron emission tomography cerebrospinal fluid biomarkers plasma biomarkers |
| title | Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease |
| title_full | Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease |
| title_fullStr | Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease |
| title_full_unstemmed | Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease |
| title_short | Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease |
| title_sort | cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in alzheimer s disease |
| topic | Alzheimer disease amyloid positron emission tomography cerebrospinal fluid biomarkers plasma biomarkers |
| url | https://doi.org/10.15252/emmm.201911170 |
| work_keys_str_mv | AT sebastianpalmqvist cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT philipsinsel cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT erikstomrud cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT shorenajanelidze cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT henrikzetterberg cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT brittabrix cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT udoeichenlaub cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT jeffreyldage cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT xiyunchai cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT kajblennow cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT niklasmattsson cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease AT oskarhansson cerebrospinalfluidandplasmabiomarkertrajectorieswithincreasingamyloiddepositioninalzheimersdisease |