What question did this study set out to answer?

This research aims to assess astrocyte reactivity across the Alzheimer's disease (AD) continuum and its relationship with amyloid burden.

May 15, 2026European Journal of Nuclear Medicine and Molecular Imaging0 citationsOpen Access

Astrocyte reactivity across the AD continuum measured by 18FSMBT-1 and its relationship with the Aβ burden

YWYingying Wu KHKotaro Hiraoka BMBerihu Mesfin

Key Points

This research aims to assess astrocyte reactivity across the Alzheimer's disease (AD) continuum and its relationship with amyloid burden.
Utilized [18F]SMBT-1 PET imaging data for subgroup comparisons based on Aβ status.
Stratified participants by amyloid positivity (MCI+ and HC-) and assessed regional uptake in defined brain regions.
Analyzed correlations between regional SMBT-1 uptake and cognitive scores.
Significantly higher SMBT-1 uptake in amyloid-positive MCI and AD groups compared to amyloid-negative HC, particularly in frontal and temporal regions.
Distinct astrocyte reactivity patterns were observed in different MCI subtypes, with MCI+ showing a widespread AD-like pattern.
Higher uptake in symptomatic MCI+ individuals contrasted with asymptomatic HC+ individuals, correlating with greater Aβ burden and lower cognitive scores.

Abstract

PURPOSE: F]SMBT-1, while exploring its association with cognitive performance and amyloid burden. METHODS: F]SMBT-1 PET data using four reference regions for subgroup comparisons stratified by Aβ status. RESULTS: F]SMBT-1 uptake was significantly elevated in amyloid-positive MCI (MCI+) and AD groups compared with amyloid-negative HC (HC-) in the frontal, temporal, and posterior cingulate regions. Notably, astrogliosis patterns distinguished MCI subtypes: MCI+ individuals exhibited a widespread AD-like pattern, whereas the MCI- group showed a distinct profile. Furthermore, the uptake in symptomatic MCI+ individuals was significantly higher than that in asymptomatic HC+ individuals. Regional SMBT-1 uptake also strongly correlated with greater Aβ burden and worse cognitive scores. CONCLUSION: F]SMBT-1 is a promising tool for characterizing the spatial pattern and magnitude of reactive astrogliosis across the Aβ-defined AD continuum. Our findings further suggest that astrogliosis may represent an important mechanistic link between amyloid pathology and cognitive impairment, supporting its potential relevance in therapeutic development. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs031210602, registered Feb. 07, 2022. URL FOR THE TRIAL REGISTRY: https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031210602 .

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