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metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 118 adults with Down syndrome from the Down Alzheimer Barcelona Imaging Initiative and 71 euploid healthy controls from the Sant Pau Initiative on Neurodegeneration cohort. We measured the levels of myo\u2010inositol (a marker of neuroinflammation) and N\u2010acetyl\u2010aspartate (a marker of neuronal integrity) in the precuneus using magnetic resonance spectroscopy. We investigated the changes with age and along the disease continuum (asymptomatic, prodromal Alzheimer's disease, and Alzheimer's disease dementia stages). We assessed the relationship between these metabolites and A\u03b2<jats:sub>42<\/jats:sub>\/A\u03b2<jats:sub>40<\/jats:sub> ratio, phosphorylated tau\u2010181, neurofilament light (NfL), and YKL\u201040 cerebrospinal fluid levels as well as amyloid positron emission tomography uptake using Spearman correlations controlling for multiple comparisons. Finally, we computed the relationship between cortical thickness and metabolite levels using Freesurfer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Asymptomatic adults with Down syndrome had a 27.5% increase in the levels of myo\u2010inositol, but equal levels of N\u2010acetyl\u2010aspartate compared to euploid healthy controls. With disease progression, myo\u2010inositol levels increased, whereas N\u2010acetyl\u2010aspartate levels decreased in symptomatic stages of the disease. Myo\u2010inositol was associated with amyloid, tau, and neurodegeneration markers, mainly at symptomatic stages of the disease, whereas N\u2010acetyl\u2010aspartate was related to neurodegeneration biomarkers in symptomatic stages. Both metabolites were significantly associated with cortical thinning, mainly in symptomatic participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Magnetic resonance spectroscopy detects Alzheimer's disease related inflammation and neurodegeneration, and could be a good noninvasive disease\u2010stage biomarker in Down syndrome. 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