Abstract
Metabolomics has demonstrated a great potential in numerous biomedical research fields in the last years, such as the study of the underlying pathology of diseases, discovery of diagnostic biomarkers or drug development. Nowadays, the main challenge in metabolomics is to obtain comprehensive and unbiased metabolomic profiles due to the huge complexity, heterogeneity and dynamism of metabolome. For this purpose, mass spectrometry represents a very interesting analytical platform, since complexity of metabolome may be overcome through the use of different orthogonal separation techniques, including liquid chromatography, gas chromatography and capillary electrophoresis. Alternatively, direct mass spectrometry analysis, either by direct infusion or flow injection, has been postulated as an alternative in metabolomics, complementing hyphenated approaches. These techniques exhibit several advantages such as the ability for high-throughput screening, fast analysis and wide metabolomic coverage, since there is not exclusion of compounds due to the separation device. The present work explores the potential of metabolomic platforms based on direct infusion mass spectrometry for metabolic fingerprinting of serum samples. The most important issues to be considered in this type of approaches were reviewed, including sample handling, comprehensive analysis, data processing, as well as further identification of metabolites and global characterization of metabolomic fingerprints.
Highlights
Graphical AbstractAbstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder, but nowadays there is no cure mainly because its etiology is still unclear
Alzheimer’s disease (AD): most common neurodegenerative disorder among older people Insidious onset Progressive decline of cognitive functionsMild cognitive impairment (MCI) Incipient dementia Preclinical phase of ADEtiology of Alzheimers disease Loss of neurons and synapses Unknown causes Multifactorial pathology Systemic diseaseDiagnosis via clinical criteria (NINCDSADRDA*)
With the aim to get a comprehensive overview of pathological mechanisms associated with AD, complementary metabolomic platforms were developed, including screening procedures based on direct mass spectrometry analysis and hyphenated approaches with orthogonal separation mechanisms such as liquid chromatography, gas chromatography and capillary electrophoresis
Summary
Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder, but nowadays there is no cure mainly because its etiology is still unclear. With the aim to get a comprehensive overview of pathological mechanisms associated with AD, complementary metabolomic platforms were developed, including screening procedures based on direct mass spectrometry analysis and hyphenated approaches with orthogonal separation mechanisms such as liquid chromatography, gas chromatography and capillary electrophoresis. The application of these techniques to serum samples from patients suffering from Alzheimer’s disease and mild cognitive impairment enabled the identification of numerous metabolic alterations linked to pathogenesis of this disorder and its progression from pre-clinical stages, including abnormalities in the composition of membrane lipids, deficits in energy metabolism and neurotransmission, and oxidative stress, among others. Alterations detected in peripheral organs confirm the systemic nature of this neurodegenerative disorder
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