Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study

In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways. Methods and findingsWe first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD:n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]:n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations wi th severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD,p = 0.003; S-adenosyl methionine: higher in AD,p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD,p

Source: PLoS Medicine - January 23, 2020 Category: Internal Medicine Authors: Uma V. Mahajan Source Type: research