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http://hdl.handle.net/10609/149483
Títol: | Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome |
Autoria: | Montal, Victor Barroeta, Isabel Bejanin, Alexandre Pegueroles, Jordi Carmona Iragui, Maria ALTUNA-AZKARGORTA, MIREN Benejam, Bessy Videla Toro, Laura Fernández, Susana Padilla, Concepcion Aranha, Mateus Iulita, M. Florencia Vidal-Piñeiro, Didac Alcolea, Daniel Blesa, Rafael Lleó, Alberto Fortea, Juan Down Alzheimer Barcelona Neuroimaging Initiative |
Resum: | Objective The purpose of this study was to examine the Alzheimer's disease metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness. Methods 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-inositol (a marker of neuroinflammation) and N-acetyl-aspartate (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 Aβ42/Aβ40 ratio, phosphorylated tau-181, neurofilament light (NfL), and YKL-40 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. Results Asymptomatic adults with Down syndrome had a 27.5% increase in the levels of myo-inositol, but equal levels of N-acetyl-aspartate compared to euploid healthy controls. With disease progression, myo-inositol levels increased, whereas N-acetyl-aspartate levels decreased in symptomatic stages of the disease. Myo-inositol was associated with amyloid, tau, and neurodegeneration markers, mainly at symptomatic stages of the disease, whereas N-acetyl-aspartate was related to neurodegeneration biomarkers in symptomatic stages. Both metabolites were significantly associated with cortical thinning, mainly in symptomatic participants. Interpretation Magnetic resonance spectroscopy detects Alzheimer's disease related inflammation and neurodegeneration, and could be a good noninvasive disease-stage biomarker in Down syndrome. |
DOI: | https://doi.org/10.1002/ana.26178 |
Tipus de document: | info:eu-repo/semantics/article |
Versió del document: | info:eu-repo/semantics/acceptedVersion |
Data de publicació: | 2-set-2021 |
Apareix a les col·leccions: | Articles Articles cientÍfics |
Arxius per aquest ítem:
Arxiu | Descripció | Mida | Format | |
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Montal_AnnalsNeurology_Metabolite.pdf | 1,56 MB | Adobe PDF | Veure/Obrir |
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