Background: Differential diagnosis of people presenting with mild cognitive impairment (MCI) that will progress to Alzheimer's disease (AD) remains clinically challenging. Current criteria used to define AD include a series of neuropsychological assessments together with relevant imaging analysis such as magnetic resonance imaging (MRI). The clinical sensitivity and specificity of these assessments would be improved by the concomitant use of novel serum biomarkers. The branched chain aminotransferase proteins (BCAT) are potential candidates as they are significantly elevated in AD brain, correlate with Braak Stage, and may have a role in AD pathology.
Objective: In this hypothesis-driven project, we aimed to establish if serum BCAT and its metabolites are significantly altered in AD participants and assess their role as markers of disease pathology.
Methods: Serum amino acids were measured using a triple quadrupole mass spectrometer for tandem mass spectroscopy together with BCAT levels using western blot analysis, coupled with neuropsychological assessments and MRI.
Results: We present data supporting a substantive mutually correlated system between BCAT and glutamate, neuropsychological tests, and MRI for the diagnosis of AD. These three domains, individually, and in combination, show good utility in discriminating between groups. Our model indicates that BCAT and glutamate accurately distinguish between control and AD participants and in combination with the neuropsychological assessment, MoCA, improved the overall sensitivity to 1.00 and specificity to 0.978.
Conclusion: These findings indicate that BCAT and glutamate have potential to improve the clinical utility and predictive power of existing methods of AD assessment and hold promise as early indicators of disease pathology.
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http://dx.doi.org/10.3233/JAD-180879 | DOI Listing |
Molecules
December 2024
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate.
View Article and Find Full Text PDFJ Histochem Cytochem
September 2024
Department of Biochemistry, College of Science.
Branched-chain amino acids (BCAAs) play vital roles in metabolic and physiological processes, with their catabolism initiated by two branched-chain aminotransferase isozymes: cytosolic (BCATc) and mitochondrial (BCATm). These enzymes have tissue and cell-specific compartmentalization and are believed to shuttle metabolites between cells and tissues. Although their expression and localization have been established in most tissues, ocular tissues remain unknown.
View Article and Find Full Text PDFBiotechnol J
June 2023
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Hydrolysates are used as media supplements although their role is not well characterized. In this study, cottonseed hydrolysates, which contained peptides and galactose as supplemental substrates, were added to Chinese hamster ovary (CHO) batch cultures, enhancing cell growth, immunoglobulin (IgG) titers, and productivities. Extracellular metabolomics coupled with tandem mass tag (TMT) proteomics revealed metabolic and proteomic changes in cottonseed-supplemented cultures.
View Article and Find Full Text PDFFront Pharmacol
November 2022
Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular Renal and Metabolism (CVRM), BioPharmaceutical R&D AstraZeneca, Gothenburg, Sweden.
Abnormal branched-chained amino acids (BCAA) accumulation in cardiomyocytes is associated with cardiac remodeling in heart failure. Administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 has been shown to reduce cardiac BCAA levels and demonstrated positive effects on cardiac function in a preclinical setting. The current study is focused on evaluating the impact of BT2 on the systemic and cardiac levels of BCAA and their metabolites as well as activities of BCAA catabolic enzymes using a quantitative systems pharmacology model.
View Article and Find Full Text PDFBMC Plant Biol
December 2021
Key Laboratory of Ministry of Education for Genetics, Breeding and Multiple Utilization of Crops, College of Agriculture, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.
Background: Light quality severely affects biosynthesis and metabolism-associated process of glutathione. However, the role of specific light is still unclear on the glutathione metabolism. In this article, comparatively transcriptome and metabolome methods are used to fully understand the blue and red-light conditions working on the glutathione metabolism in maize seedling leaf.
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