Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease

Bhawal, Ruchika; Fu, Qin; Anderson, Elizabeth T.; Gibson, Gary E.; Zhang, Sheng

doi:10.3390/ijms222413188

Cited by 14 publications

(8 citation statements)

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“…Metabolomics is an emerging approach in life science and precision medicine for biomarker discovery in various neurodegenerative diseases such as MS.(Bhargava and Calabresi 2016; Noga et al 2012) Previous studies showed that specific altered metabolites and lipids in plasma samples varied with AD progression. (Bhawal et al 2021) The metabolomic profile of the produced plasma patterns revealed many significantly changing metabolites in different MS types particularly RRMS and SPMS (red dots in Supplementary Figure 13 ) in all the layers. For example, it has been reported that glutamate may be related to inflammatory and neurodegenerative processes evident in MS.(Kostic et al 2013; Pitt et al 2000) We have also found that glucoheptonic acid metabolite is significantly different in layers one and two of the produced plasma patterns within the MagLev system.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Analysis of Magnetically Levitated Plasma Biomolecules

Ashkarran

Gharibi

Zeki

et al. 2022

Preprint

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We recently discovered that superparamagnetic iron oxide nanoparticles (SPIONs) can levitate plasma biomolecules in the magnetic levitation (MagLev) system and cause formation of ellipsoidal biomolecular bands. To better understand the composition of the levitated biomolecules in various bands, we comprehensively characterized them by multi-omics analyses. To probe whether the biomolecular composition of the levitated ellipsoidal bands correlates with the health of plasma donors, we used plasma from individuals who had various types of multiple sclerosis (MS), as a model disease with significant clinical importance. Our findings reveal that, while the composition of proteins does not show much variability, there are significant differences in the lipidome and metabolome profiles of each magnetically levitated ellipsoidal band. By comparing the lipidome and metabolome compositions of various plasma samples, we found that the levitated biomolecular ellipsoidal bands do contain information on the health status of the plasma donors. More specifically, we demonstrate that there are particular lipids and metabolites in various layers of each specific plasma pattern that significantly contribute to the discrimination of different MS subtypes, i.e., relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), and primary-progressive MS (PPMS). These findings will pave the way for utilization of MagLev of biomolecules in biomarker discovery and diagnosis of this and other complex disorders.

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Section: Discussionmentioning

confidence: 99%

Multi-Omics Analysis of Magnetically Levitated Plasma Biomolecules

Ashkarran

Gharibi

Zeki

et al. 2022

Preprint

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“…Similar to these results, most PCs were upregulated in the plasma of APP/PS1 mice in the present study. In fact, researches on the levels of PCs in AD were not uniform and the results were somewhat controversial ( Toledo et al, 2017 ; Huo et al, 2020 ; Bhawal et al, 2021 ). These contrary findings could arise by diverse functions of different PCs, which can be responsible for the minority of decreased PCs in our study.…”

Section: Discussionmentioning

confidence: 99%

“…For the lipidomic analysis, acquired MS/MS data were processed using Thermo Scientific LipidSearch 4.2 software for peak detection, lipid annotation, peak alignment, and relative quantitation ( Bhawal et al, 2021 ). The main parameters were set as follows: precursor tolerance, 5 ppm; product tolerance, 5 ppm; intensity threshold for product ion, 5.0%.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer’s disease

et al. 2022

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Introduction:Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer’s disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism.Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE.Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aβ) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p<0.05), which were considered as potential therapeutic targets of GBLE on AD. The response of APP/PS1 mice to GBLE was similar to that of donepezil, which significantly reversed the levels of 23 disturbed metabolites and 30 lipids.Discussion: Our data suggested that lipid metabolism was dramatically perturbed in the plasma of APP/PS1 mice, and GBLE might exert its neuroprotective effects by restoring lipid metabolic balance. This work provided a basis for better understanding the potential pathogenesis of AD and shed new light on the therapeutic mechanism of GBLE in the treatment of AD.

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“…To mitigate the long-term effects of metabolic disorders, healthcare providers rely on a wide range of interventions. These interventions may include lifestyle changes, such as changes in diet and exercise habits, as well as medication to manage symptoms and prevent further health complications [ 6 , 7 ]. In recent years, the development of high-resolution molecular tools has allowed for a more accurate detection and diagnosis of metabolic disorders by examining the leading and lagging indicators in patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

Latif,

Hashmi,

Alayoubi

et al. 2024

JCM

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Background and Objectives: Inherited metabolic disorders (IMDs) are a group of genetic disorders characterized by defects in enzymes or transport proteins involved in metabolic processes. These defects result in an abnormal accumulation of metabolites and thus interfere with the body’s metabolism. A variety of IMDs exist and differential diagnosis is often challenging. Our objective was to gain insight into the genetic basis of IMDs and the correlations between specific genetic mutations and clinical presentations in patients admitted at various hospitals in the Madinah region of the Kingdom of Saudi Arabia. Material and Methods: Whole exome sequencing (WES) has emerged as a powerful tool for diagnosing IMDs and allows for the identification of disease-causing genetic mutations in individuals suspected of IMDs. This ensures accurate diagnosis and appropriate management. WES was performed in four families with multiple individuals showing clinical presentation of IMDs. Validation of the variants identified through WES was conducted using Sanger sequencing. Furthermore, various computational analyses were employed to uncover the disease gene co-expression and metabolic pathways. Results: Exome variant data analysis revealed missense variants in the BTD (c.1270G > C), ASL (c.1300G > T), GBE1 (c.985T > G) and AGL (c.113C > G) genes. Mutations in these genes are known to cause IMDs. Conclusions: Thus, our data showed that exome sequencing, in conjunction with clinical and biochemical characteristics and pathological hallmarks, could deliver an accurate and high-throughput outcome for the diagnosis and sub-typing of IMDs. Overall, our findings emphasize that the integration of WES with clinical and pathological information has the potential to improve the diagnosis and understanding of IMDs and related disorders, ultimately benefiting patients and the medical community.

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Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease

Cited by 14 publications

References 57 publications

Multi-Omics Analysis of Magnetically Levitated Plasma Biomolecules

Multi-Omics Analysis of Magnetically Levitated Plasma Biomolecules

Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer’s disease

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

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