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

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

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14 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)615-628
Number of pages14
JournalJournal of Alzheimer's Disease
Volume92
Issue number2
DOIs
Publication statusPublished - 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Astrocyte reactivity
  • biomarkers
  • 18F-SMBT-1
  • glial fibrillary acidic protein
  • monoamine oxidase B
  • positron emission tomography

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