Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer’s Disease

Author:

Chatterjee Pratishtha12,Doré Vincent34,Pedrini Steve25,Krishnadas Natasha46,Thota Rohith17,Bourgeat Pierrick8,Ikonomovic Milos D.910,Rainey-Smith Stephanie R.211512,Burnham Samantha C.8,Fowler Christopher6,Taddei Kevin25,Mulligan Rachel4,Ames David1314,Masters Colin L.6,Fripp Jürgen3,Rowe Christopher C.415,Martins Ralph N.12516,Villemagne Victor L.417,

Affiliation:

1. Macquarie Medical School, Macquarie University, North Ryde, NSW, Australia

2. School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia

3. The Australian eHealth Research Centre, CSIRO, Brisbane, QLD, Australia

4. Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, VIC, Australia

5. Australian Alzheimer’s Research Foundation, Sarich Neuroscience Research Institute, Nedlands, WA, Australia

6. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia

7. School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW, Australia

8. Health and Biosecurity Flagship, Australian eHealth Research Centre, Herston, QLD, Australia

9. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

10. Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA

11. Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, WA, Australia

12. School of Psychological Science, University of Western Australia, Crawley, WA, Australia

13. National Ageing Research Institute, Parkville, VIC, Australia

14. Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, VIC, Australia

15. The Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia

16. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia

17. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

Abstract

Background: Astrocyte reactivity is an early event along the Alzheimer’s disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD. Objective: The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers. Methods: Plasma GFAP and Aβ were measured using the Simoa® platform in participants who underwent brain 18F-SMBT-1 and Aβ–PET imaging, comprising 54 healthy control (13 Aβ–PET+ and 41 Aβ–PET–), 11 mild cognitively impaired (3 Aβ–PET+ and 8 Aβ–PET–) and 6 probable AD (5 Aβ–PET+ and 1 Aβ–PET–) individuals. Linear regressions were used to assess associations of interest. Results: Plasma GFAP was associated with 18F-SMBT-1 signal in brain regions prone to early Aβ deposition in AD, such as the supramarginal gyrus (SG), posterior cingulate (PC), lateral temporal (LT) and lateral occipital cortex (LO). After adjusting for age, sex, APOE ɛ4 genotype, and soluble Aβ (plasma Aβ42/40 ratio), plasma GFAP was associated with 18F-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE ɛ4 genotype and insoluble Aβ (Aβ–PET), plasma GFAP was associated with 18F-SMBT-1 signal in the SG. Conclusion: There is an association between plasma GFAP and regional 18F-SMBT-1 PET, and this association appears to be dependent on brain Aβ load.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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