High‐resolution metabolomic profiling of Alzheimer’s disease in plasma
Abstract Background Alzheimer’s disease (AD) is a complex neurological disorder with contributions from genetic and environmental factors. High‐resolution metabolomics (HRM) has the potential to identify novel endogenous and environmental factors involved in AD. Previous metabolomics studies have id...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.50956 |
| _version_ | 1818608822867984384 |
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| author | Megan M. Niedzwiecki Douglas I. Walker Jennifer Christina Howell Kelly D. Watts Dean P. Jones Gary W. Miller William T. Hu |
| author_facet | Megan M. Niedzwiecki Douglas I. Walker Jennifer Christina Howell Kelly D. Watts Dean P. Jones Gary W. Miller William T. Hu |
| author_sort | Megan M. Niedzwiecki |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a complex neurological disorder with contributions from genetic and environmental factors. High‐resolution metabolomics (HRM) has the potential to identify novel endogenous and environmental factors involved in AD. Previous metabolomics studies have identified circulating metabolites linked to AD, but lack of replication and inconsistent diagnostic algorithms have hindered the generalizability of these findings. Here we applied HRM to identify plasma metabolic and environmental factors associated with AD in two study samples, with cerebrospinal fluid (CSF) biomarkers of AD incorporated to achieve high diagnostic accuracy. Methods Liquid chromatography‐mass spectrometry (LC–MS)‐based HRM was used to identify plasma and CSF metabolites associated with AD diagnosis and CSF AD biomarkers in two studies of prevalent AD (Study 1: 43 AD cases, 45 mild cognitive impairment [MCI] cases, 41 controls; Study 2: 50 AD cases, 18 controls). AD‐associated metabolites were identified using a metabolome‐wide association study (MWAS) framework. Results An MWAS meta‐analysis identified three non‐medication AD‐associated metabolites in plasma, including elevated levels of glutamine and an unknown halogenated compound and lower levels of piperine, a dietary alkaloid. The non‐medication metabolites were correlated with CSF AD biomarkers, and glutamine and the unknown halogenated compound were also detected in CSF. Furthermore, in Study 1, the unknown compound and piperine were altered in MCI patients in the same direction as AD dementia. Conclusions In plasma, AD was reproducibly associated with elevated levels of glutamine and a halogen‐containing compound and reduced levels of piperine. These findings provide further evidence that exposures and behavior may modify AD risks. |
| first_indexed | 2024-12-16T14:48:45Z |
| format | Article |
| id | doaj.art-e51ef293ea304ab1bcb808a1ccb78c7c |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-16T14:48:45Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-e51ef293ea304ab1bcb808a1ccb78c7c2022-12-21T22:27:40ZengWileyAnnals of Clinical and Translational Neurology2328-95032020-01-0171364510.1002/acn3.50956High‐resolution metabolomic profiling of Alzheimer’s disease in plasmaMegan M. Niedzwiecki0Douglas I. Walker1Jennifer Christina Howell2Kelly D. Watts3Dean P. Jones4Gary W. Miller5William T. Hu6Department of Environmental Health Rollins School of Public Health Emory University Atlanta GeorgiaDepartment of Environmental Health Rollins School of Public Health Emory University Atlanta GeorgiaDepartment of Neurology Emory University Atlanta GeorgiaDepartment of Neurology Emory University Atlanta GeorgiaClinical Biomarkers Laboratory Division of Pulmonary, Allergy Critical Care and Sleep Medicine Emory University Atlanta GeorgiaDepartment of Environmental Health Rollins School of Public Health Emory University Atlanta GeorgiaDepartment of Neurology Emory University Atlanta GeorgiaAbstract Background Alzheimer’s disease (AD) is a complex neurological disorder with contributions from genetic and environmental factors. High‐resolution metabolomics (HRM) has the potential to identify novel endogenous and environmental factors involved in AD. Previous metabolomics studies have identified circulating metabolites linked to AD, but lack of replication and inconsistent diagnostic algorithms have hindered the generalizability of these findings. Here we applied HRM to identify plasma metabolic and environmental factors associated with AD in two study samples, with cerebrospinal fluid (CSF) biomarkers of AD incorporated to achieve high diagnostic accuracy. Methods Liquid chromatography‐mass spectrometry (LC–MS)‐based HRM was used to identify plasma and CSF metabolites associated with AD diagnosis and CSF AD biomarkers in two studies of prevalent AD (Study 1: 43 AD cases, 45 mild cognitive impairment [MCI] cases, 41 controls; Study 2: 50 AD cases, 18 controls). AD‐associated metabolites were identified using a metabolome‐wide association study (MWAS) framework. Results An MWAS meta‐analysis identified three non‐medication AD‐associated metabolites in plasma, including elevated levels of glutamine and an unknown halogenated compound and lower levels of piperine, a dietary alkaloid. The non‐medication metabolites were correlated with CSF AD biomarkers, and glutamine and the unknown halogenated compound were also detected in CSF. Furthermore, in Study 1, the unknown compound and piperine were altered in MCI patients in the same direction as AD dementia. Conclusions In plasma, AD was reproducibly associated with elevated levels of glutamine and a halogen‐containing compound and reduced levels of piperine. These findings provide further evidence that exposures and behavior may modify AD risks.https://doi.org/10.1002/acn3.50956 |
| spellingShingle | Megan M. Niedzwiecki Douglas I. Walker Jennifer Christina Howell Kelly D. Watts Dean P. Jones Gary W. Miller William T. Hu High‐resolution metabolomic profiling of Alzheimer’s disease in plasma Annals of Clinical and Translational Neurology |
| title | High‐resolution metabolomic profiling of Alzheimer’s disease in plasma |
| title_full | High‐resolution metabolomic profiling of Alzheimer’s disease in plasma |
| title_fullStr | High‐resolution metabolomic profiling of Alzheimer’s disease in plasma |
| title_full_unstemmed | High‐resolution metabolomic profiling of Alzheimer’s disease in plasma |
| title_short | High‐resolution metabolomic profiling of Alzheimer’s disease in plasma |
| title_sort | high resolution metabolomic profiling of alzheimer s disease in plasma |
| url | https://doi.org/10.1002/acn3.50956 |
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