Metabolic network failures in Alzheimer's disease: A biochemical road map.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Toledo Jon B, Arnold Matthias, Kastenmüller Gabi, Chang Rui, Baillie Rebecca A, Han Xianlin, Thambisetty Madhav, Tenenbaum Jessica D, Suhre Karsten, Thompson J Will, John-Williams Lisa St, MahmoudianDehkordi Siamak, Rotroff Daniel M, Jack John R, Motsinger-Reif Alison, Risacher Shannon L, Blach Colette, Lucas Joseph E, Massaro Tyler, Louie Gregory, Zhu Hongjie, Dallmann Guido, Klavins Kristaps, Koal Therese, Kim Sungeun, Nho Kwangsik, Shen Li, Casanova Ramon, Varma Sudhir, Legido-Quigley Cristina, Moseley M Arthur, Zhu Kuixi, Henrion Marc Y R, van der Lee Sven J, Harms Amy C, Demirkan Ayse, Hankemeier Thomas, van Duijn Cornelia M, Trojanowski John Q, Shaw Leslie M, Saykin Andrew J, Weiner Michael W, Doraiswamy P Murali, Kaddurah-Daouk Rima, Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Аннотация
METHODS: Fasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted.
RESULTS: Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ1-42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease.
DISCUSSION: Metabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.