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

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 theADcontinuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using F-18-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 andA beta were measured using the Simoa((R)) platform in participants who underwent brain F-18-SMBT-1 and A beta-PET imaging, comprising 54 healthy control (13 A beta-PET+ and 41 A beta-PET-), 11 mild cognitively impaired (3 A beta-PET+ and 8 A beta-PET-) and 6 probable AD (5 A beta-PET+ and 1 A beta-PET-) individuals. Linear regressions were used to assess associations of interest. Results: Plasma GFAP was associated with F-18-SMBT-1 signal in brain regions prone to early A beta 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 beta 4 genotype, and soluble A beta (plasma A beta 42/40 ratio), plasma GFAP was associated with F-18-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE beta 4 genotype and insoluble A beta (A beta-PET), plasma GFAP was associated with F-18-SMBT-1 signal in the SG. Conclusion: There is an association between plasma GFAP and regional F-18-SMBT-1 PET, and this association appears to be dependent on brain A beta load.

Automated summary

Astrocyte reactivity is associated with the elevation of plasma glial fibrillary acidic protein (GFAP) and monoamine oxidase-B (MAO-B) in Alzheimer's disease. The association between plasma GFAP and regional F-18-SMBT-1 PET is dependent on brain β-amyloid (Aβ) load.