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This study aimed to assess astrocyte reactivity <jats:italic>in\u2009vivo<\/jats:italic> in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 30 patients with PSP\u2010Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through <jats:sup>18<\/jats:sup>F\u2010florzolotau positron emission tomography. Myo\u2010inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The levels of myo\u2010inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05); these increases were significantly associated with PSP rating scale and cognitive function scores (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The lactate level was high in patients, and correlated significantly with high myo\u2010inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo\u2010inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. 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