Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome
Por:
Montal, V, Barroeta, I, Bejanin, A, Pegueroles, J, Carmona-Iragui, M, Altuna, M, Benejam, B, Videla, L, Fernandez, S, Padilla, C, Aranha, MR, Iulita, MF, Vidal-Pineiro, D, Alcolea, D, Blesa, R, Lleo, A, Fortea, J
Publicada:
1 sep 2021
Ahead of Print:
1 ago 2021
Resumen:
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 A beta(42)/A beta(40) 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
Filiaciones:
Montal, V:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Barroeta, I:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Bejanin, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Pegueroles, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Carmona-Iragui, M:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Altuna, M:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Benejam, B:
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Videla, L:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Fernandez, S:
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Padilla, C:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Aranha, MR:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Iulita, MF:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Vidal-Pineiro, D:
Univ Oslo, Ctr Lifespan Changes Brain & Cognit, Dept Psychol, Oslo, Norway
Alcolea, D:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Blesa, R:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
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