[18F]SMBT‐1 PET as an Imaging Biomarker for Reactive Astrogliosis in Mild Cognitive Impairment and Alzheimer's Disease

TL;DR

A new PET scan called [18F]SMBT-1 can detect brain changes linked to reactive astrogliosis in Alzheimer's and mild cognitive impairment, aligning with amyloid buildup and blood markers.

Contribution

This study introduces [18F]SMBT-1 as a novel PET tracer for imaging reactive astrogliosis in Alzheimer's disease and mild cognitive impairment.

Findings

[18F]SMBT-1 binding was significantly higher in amyloid-positive MCI and AD patients compared to controls in brain regions associated with reactive astrogliosis.

Plasma GFAP levels were elevated in MCI and AD patients with increased [18F]SMBT-1 binding in the neocortex.

The tracer's signal overlapped with amyloid accumulation and showed consistency with plasma biomarker results.

Abstract

[18F]SMBT‐1, a PET tracer targeting monoamine oxidase B (MAO‐B), was developed to visualize reactive astrogliosis in the brain. This study investigated [18F]SMBT‐1 binding in the brains of patients with Alzheimer's disease (AD) and its association with plasma biomarkers.

We performed [18F]SMBT‐1 scans in 35 healthy elderly controls (HCs), 44 patients with mild cognitive impairment (MCI), and 13 patients with Alzheimer's disease (AD). To compare the regional standardized uptake value ratio (SUVR) between the disease groups, 30‐minute dynamic scans were conducted 60 min after administration of [18F]SMBT‐1. PiB PET or flutemetamol PET was performed to confirm the presence of amyloid‐β (Aβ) pathology in the brain. Plasma biomarkers (GFAP, pTau‐217, NfL) were measured in 38 subjects who underwent SMBT‐1 PET.

Compared to the amyloid‐negative HC and MCI groups, [18F]SMBT‐1 accumulation was significantly increased in many brain regions, including the temporal, parietal, occipital, cingulate, and parahippocampal gyri, in amyloid‐positive MCI and AD patients. These brain regions coincided with regions considered to be frequent sites of reactive astrogliosis in the AD continuum and overlapped with Aβ accumulation. Plasma GFAP was elevated in MCI and AD patients who showed the elevation of [18F]SMBT‐1 binding in the neocortex.

[18F]SMBT‐1 binding in the neocortex was elevated in patients with MCI and AD in association with Aβ accumulation, which is consistent with the results of plasma GFAP measurements. These findings suggest that [18F]SMBT‐1 PET is a useful biomarker of reactive astrogliosis in the brain.