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This multicenter study aimed to investigate the progression of astrocyte reactivity across the AD continuum, including healthy controls (HC), mild cognitive impairment (MCI), and AD, using the novel monoamine oxidase B (MAO-B)-specific PET tracer [\n                      <jats:sup>18<\/jats:sup>\n                      F]SMBT-1, while exploring its association with cognitive performance and amyloid burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 91 participants (35 HC, 44 MCI, 12 AD) underwent [\n                      <jats:sup>18<\/jats:sup>\n                      F]SMBT-1 PET, amyloid PET, T1-weighted MRI, and standardized neuropsychological assessments. Standardized uptake value ratios (SUVRs) were calculated based on [\n                      <jats:sup>18<\/jats:sup>\n                      F]SMBT-1 PET data using four reference regions for subgroup comparisons stratified by A\u03b2 status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]SMBT-1 uptake was significantly elevated in amyloid-positive MCI (MCI+) and AD groups compared with amyloid-negative HC (HC\u2212) 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\u2212 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 A\u03b2 burden and worse cognitive scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that [\n                      <jats:sup>18<\/jats:sup>\n                      F]SMBT-1 is a promising tool for characterizing the spatial pattern and magnitude of reactive astrogliosis across the A\u03b2-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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>Japan Registry of Clinical Trials (jRCT) jRCTs031210602, registered Feb. 07, 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>URL for the trial registry<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/jrct.mhlw.go.jp\/en-latest-detail\/jRCTs031210602\" ext-link-type=\"uri\">https:\/\/jrct.mhlw.go.jp\/en-latest-detail\/jRCTs031210602<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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This study was approved by the Tokyo Metropolitan Geriatric Medical Center Clinical Research Review Board (registration ID: jRCTs031210602).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors affirmed that all human research participants provided informed consent for their data and images to be published in an anonymized format.","order":3,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ryuichi Harada, Shozo Furumoto, and Nobuyuki Okamura have a patents pending for the [\u00b9\u2078F]SMBT-1 molecule described in this article. Nobuyuki Okamura owns stock at Clino Ltd. The authors declare no other potential conflicts of interest relevant to this study.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}