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Article

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

1
Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY 14853, USA
2
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA
3
Burke Neurological Institute, White Plains, NY 10605, USA
*
Author to whom correspondence should be addressed.
Academic Editor: C. Michael Greenlief
Int. J. Mol. Sci. 2021, 22(24), 13188; https://doi.org/10.3390/ijms222413188
Received: 21 October 2021 / Revised: 24 November 2021 / Accepted: 1 December 2021 / Published: 7 December 2021
(This article belongs to the Special Issue Biological Systems at the Protein Level 2.0)
Serum metabolomics and lipidomics are powerful approaches for discovering unique biomarkers in various diseases and associated therapeutics and for revealing metabolic mechanisms of both. Treatment with Benfotiamine (BFT), a thiamine prodrug, for one year produced encouraging results for patients with mild cognitive impairment and mild Alzheimer’s disease (AD). In this study, a parallel metabolomics and lipidomics approach was applied for the first exploratory investigation on the serum metabolome and lipidome of patients treated with BFT. A total of 315 unique metabolites and 417 lipids species were confidently identified and relatively quantified. Rigorous statistical analyses revealed significant differences between the placebo and BFT treatment groups in 25 metabolites, including thiamine, tyrosine, tryptophan, lysine, and 22 lipid species, mostly belonging to phosphatidylcholines. Additionally, 10 of 11 metabolites and 14 of 15 lipid species reported in previous literature to follow AD progression changed in the opposite direction to those reported to reflect AD progression. Enrichment and pathway analyses show that significantly altered metabolites by BFT are involved in glucose metabolism and biosynthesis of aromatic amino acids. Our study discovered that multiple novel biomarkers and multiple mechanisms that may underlie the benefit of BFT are potential therapeutic targets in AD and should be validated in studies with larger sample sizes. View Full-Text
Keywords: metabolomics; lipidomics; Alzheimer’s disease; serum; thiamine; benfotiamine; mass spectrometry; biomarkers metabolomics; lipidomics; Alzheimer’s disease; serum; thiamine; benfotiamine; mass spectrometry; biomarkers
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MDPI and ACS Style

Bhawal, R.; Fu, Q.; Anderson, E.T.; Gibson, G.E.; Zhang, S. Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 13188. https://doi.org/10.3390/ijms222413188

AMA Style

Bhawal R, Fu Q, Anderson ET, Gibson GE, Zhang S. Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease. International Journal of Molecular Sciences. 2021; 22(24):13188. https://doi.org/10.3390/ijms222413188

Chicago/Turabian Style

Bhawal, Ruchika, Qin Fu, Elizabeth T. Anderson, Gary E. Gibson, and Sheng Zhang. 2021. "Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease" International Journal of Molecular Sciences 22, no. 24: 13188. https://doi.org/10.3390/ijms222413188

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