Astrocyte reactivity across the AD continuum measured by [18F]SMBT-1 and its relationship with the Aβ burden

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 .