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Plasma protein biomarkers for the prediction of CSF amyloid and tau and [18F]-flutemetamol PET scan result
- Source :
- Frontiers in Aging Neuroscience, 10. Frontiers Media S.A., Frontiers in Aging Neuroscience, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Frontiers in Aging Neuroscience, 10:409. Frontiers Media S.A., Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Westwood, S, Baird, A L, Hye, A, Ashton, N J, Nevado-Holgado, A J, Anand, S N, Liu, B, Newby, D, Bazenet, C, Kiddle, S J, Ward, M, Newton, B, Desai, K, Tan Hehir, C, Zanette, M, Galimberti, D, Parnetti, L, Lleó, A, Baker, S, Narayan, V A, van der Flier, W M, Scheltens, P, Teunissen, C E, Visser, P J & Lovestone, S 2018, ' Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [18F]-Flutemetamol PET Scan Result ', Frontiers in Aging Neuroscience, vol. 10, pp. 409 . https://doi.org/10.3389/fnagi.2018.00409, Frontiers in Aging Neuroscience, Vol 10 (2018)
- Publication Year :
- 2019
- Publisher :
- Frontiers Media, 2019.
-
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) Aß 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/Aß42 (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 Aß42 measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/Aß42 (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen ß 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/Aß42. 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 Aß42 (P ˜ 0.05), while both A1AT and clusterin were nominally significantly associated with CSF Aß42 (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. © Copyright © 2018 Westwood, Baird, Hye, Ashton, Nevado-Holgado, Anand, Liu, Newby, Bazenet, Kiddle, Ward, Newton, Desai, Tan Hehir, Zanette, Galimberti, Parnetti, Lleó, Baker, Narayan, van der Flier, Scheltens, Teunissen, Visser and Lovestone.
- Subjects :
- 0301 basic medicine
Oncology
Aging
MILD COGNITIVE IMPAIRMENT
BLOOD
Apolipoprotein B
Fibrinogen
0302 clinical medicine
Cerebrospinal fluid
Alzheimer’s disease
amyloid
biomarkers
blood
ficolin-2
plasma
proteomics
tau
Medicine
Cognitive decline
Original Research
INSULIN-RESISTANCE
biology
DEMENTIA
ASSOCIATION
Alzheimer's disease
SERUM-LEVELS
Blood proteins
3. Good health
ALZHEIMERS-DISEASE
Cohort
medicine.drug
medicine.medical_specialty
Amyloid
Cognitive Neuroscience
BETA
lcsh:RC321-571
03 medical and health sciences
CEREBROSPINAL-FLUID
Internal medicine
mental disorders
Dementia
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
APOLIPOPROTEIN-A-I
business.industry
medicine.disease
030104 developmental biology
biology.protein
business
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- ISSN :
- 16634365
- Database :
- OpenAIRE
- Journal :
- Frontiers in Aging Neuroscience, 10. Frontiers Media S.A., Frontiers in Aging Neuroscience, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Frontiers in Aging Neuroscience, 10:409. Frontiers Media S.A., Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Westwood, S, Baird, A L, Hye, A, Ashton, N J, Nevado-Holgado, A J, Anand, S N, Liu, B, Newby, D, Bazenet, C, Kiddle, S J, Ward, M, Newton, B, Desai, K, Tan Hehir, C, Zanette, M, Galimberti, D, Parnetti, L, Lleó, A, Baker, S, Narayan, V A, van der Flier, W M, Scheltens, P, Teunissen, C E, Visser, P J & Lovestone, S 2018, ' Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [18F]-Flutemetamol PET Scan Result ', Frontiers in Aging Neuroscience, vol. 10, pp. 409 . https://doi.org/10.3389/fnagi.2018.00409, Frontiers in Aging Neuroscience, Vol 10 (2018)
- Accession number :
- edsair.doi.dedup.....ce1d757c56dfe16a74813397a69634a9