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Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome
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 syndrom...
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Published in: | Annals of neurology 2021-09, Vol.90 (3), p.407-416 |
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Main Authors: | , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. ANN NEUROL 2021;90:407–416 |
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ISSN: | 0364-5134 1531-8249 |
DOI: | 10.1002/ana.26178 |