Metabolic profiling of Alzheimer's disease brains

Abstract

Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

“…Increased levels of three polyamines, putrescine, spermidine and spermine, have been reported in brain tissue and plasma from AD patients (Inoue et al, 2013;Trushina et al, 2013). The underlying explanation for this is that Aβ causes up-regulation of polyamine uptake and increased ornithine decarboxylase activity, which leads to increased polyamine synthesis (Yatin et al, 1999;Yatin et al, 2001).…”

Metabolomics in the Study of Alzheimer's Disease

“…In fact it can be especially useful to get the benefit from the potential to discover novel unforeseen metabolic factors or biomarkers in fingerprinting approaches with the option of demonstrating the observed changes of known metabolites or confirming the potential biomarkers by means of the metabolic profiling mode [96]. A recent study followed this comprehensive metabolomics approach in the investigation of biomarkers for AD by the comparison of postmortem brain tissue from AD patients and healthy control subjects [97]. First, a metabolic fingerprint to determine potential biomarkers and affected pathways in AD pathology was performed.…”

“…First, a metabolic fingerprint to determine potential biomarkers and affected pathways in AD pathology was performed. Then the specific metabolic pathway related to potential AD biomarkers spermine and spermidine, namely biogenic polyamine metabolism, was explored in detail finding three more molecules altered due to AD pathology [97].…”

“…It One theory suggests that the NMDA receptor excitotoxicity is caused by an excess of spermidine and spermine due to ornithine decarboxylase activity induced by plaque and/or tangle deposition in specific brain regions. (Reproduced from [97]). (Reproduced from [111]).…”

Brain Metabolomics Study on the Protective Effects of Ginsenosides Rg1 and Rb1 in an Alzheimer’s Disease Mouse Model

“…Most of these studies have been performed in biofluids because of the difficult availability of human brain tissue. Thus, only a few preliminary studies have been previously reported in this subject [12][13][14], demonstrating the potential of this approach.…”