Plasma glial fibrillary acidic protein is associated with 18F-SMBT-1 PET: Two putative astrocyte reactivity biomarkers for Alzheimer's disease

Authors

Pratishtha Chatterjee, Edith Cowan University
Vincent Doré
Steve Pedrini, Edith Cowan UniversityFollow
Natasha Krishnadas
Rohith Thota
Pierrick Bourgeat
Milos D. Ikonomovic
Stephanie R. Rainey-Smith, Edith Cowan UniversityFollow
Samantha C. Burnham
Christopher Fowler
Kevin Taddei, Edith Cowan UniversityFollow
Rachel Mulligan
David Ames
Colin L. Masters
Jürgen Fripp
Christopher C. Rowe
Ralph N. Martins, Edith Cowan UniversityFollow
Victor L. Villemagne
AIBL Research Group

Document Type

Journal Article

Publication Title

Journal of Alzheimer's disease

Volume

92

Issue

2

First Page

615

Last Page

628

PubMed ID

36776057

Publisher

IOS Press

School

School of Medical and Health Sciences

RAS ID

56537

Funders

Cooperative Research Centre (CRC) for Mental Health, an Australian Government Initiative

Pfizer International

Comments

Chatterjee, P., Doré, V., Pedrini, S., Krishnadas, N., Thota, R., Bourgeat, P., ... & Villemagne, V. L. (2023). Plasma glial fibrillary acidic protein is associated with 18F-SMBT-1 PET: Two putative astrocyte reactivity biomarkers for Alzheimer’s disease. Journal of Alzheimer's Disease, 92(2), 615-628. https://doi.org/10.3233/JAD-220908

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 Aβ_42/40 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.

DOI

10.3233/JAD-220908

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