Journal article
Plasma protein biomarkers for the prediction of CSF amyloid and tau and [18F]-flutemetamol PET scan result
- Abstract:
- Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer’s disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) Aβ and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/Aβ42 (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [18F]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF Aβ42 measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/Aβ42 (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen β chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/Aβ42. There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF Aβ42 (P ≈ 0.05), while both A1AT and clusterin were nominally significantly associated with CSF Aβ42 (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.3389/fnagi.2018.00409
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Aging Neuroscience More from this journal
- Volume:
- 10
- Article number:
- 409
- Publication date:
- 2018-12-11
- Acceptance date:
- 2018-11-28
- DOI:
- ISSN:
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1663-4365
- Keywords:
- Pubs id:
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pubs:951510
- UUID:
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uuid:de43f1a4-816a-4c8f-a94b-e5673f645422
- Local pid:
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pubs:951510
- Source identifiers:
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951510
- Deposit date:
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2018-12-11
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- Copyright holder:
- Westwood et al
- Copyright date:
- 2018
- Notes:
- Copyright © 2018 Westwood et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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