Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity
Abstract Introduction We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD). Methods Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non‐Hispani...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12025 |
| _version_ | 1798030155008966656 |
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| author | Badri Vardarajan Vrinda Kalia Jennifer Manly Adam Brickman Dolly Reyes‐Dumeyer Rafael Lantigua Iuliana Ionita‐Laza Dean P. Jones Gary W. Miller Richard Mayeux |
| author_facet | Badri Vardarajan Vrinda Kalia Jennifer Manly Adam Brickman Dolly Reyes‐Dumeyer Rafael Lantigua Iuliana Ionita‐Laza Dean P. Jones Gary W. Miller Richard Mayeux |
| author_sort | Badri Vardarajan |
| collection | DOAJ |
| description | Abstract Introduction We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD). Methods Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non‐Hispanic white (NHW) ancestry using untargeted liquid‐chromatography–based ultra‐high‐resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD‐associated metabolites. Results A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS‐DA) inferred that AD clustered separately from healthy controls (area under the curve [AUC] = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non‐essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non‐carriers (AUC = 0.9972). Discussion Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered. |
| first_indexed | 2024-04-11T19:35:40Z |
| format | Article |
| id | doaj.art-e6b5bb749a954b958c5204c7a808a7da |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-11T19:35:40Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-e6b5bb749a954b958c5204c7a808a7da2022-12-22T04:06:52ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372020-01-0161n/an/a10.1002/trc2.12025Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicityBadri Vardarajan0Vrinda Kalia1Jennifer Manly2Adam Brickman3Dolly Reyes‐Dumeyer4Rafael Lantigua5Iuliana Ionita‐Laza6Dean P. Jones7Gary W. Miller8Richard Mayeux9College of Physicians and Surgeons Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New YorkDepartment of Environmental Health Sciences Mailman School of Public Health Columbia University New York New YorkCollege of Physicians and Surgeons Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New YorkCollege of Physicians and Surgeons Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New YorkCollege of Physicians and Surgeons Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New YorkDepartment of Neurology College of Physicians and Surgeons Columbia University and the New York Presbyterian Hospital New York New YorkDepartment of Biostatistics Mailman School of Public Health Columbia University New York New YorkClinical Biomarkers Laboratory Department of Medicine Emory University Atlanta GeorgiaDepartment of Environmental Health Sciences Mailman School of Public Health Columbia University New York New YorkCollege of Physicians and Surgeons Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New YorkAbstract Introduction We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD). Methods Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non‐Hispanic white (NHW) ancestry using untargeted liquid‐chromatography–based ultra‐high‐resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD‐associated metabolites. Results A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS‐DA) inferred that AD clustered separately from healthy controls (area under the curve [AUC] = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non‐essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non‐carriers (AUC = 0.9972). Discussion Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered.https://doi.org/10.1002/trc2.12025Alzheimer's diseaseAPOE ε4metabolite profile differences in Alzheimer's diseasemetabolomicsmulti‐ethnicplasma |
| spellingShingle | Badri Vardarajan Vrinda Kalia Jennifer Manly Adam Brickman Dolly Reyes‐Dumeyer Rafael Lantigua Iuliana Ionita‐Laza Dean P. Jones Gary W. Miller Richard Mayeux Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease APOE ε4 metabolite profile differences in Alzheimer's disease metabolomics multi‐ethnic plasma |
| title | Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity |
| title_full | Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity |
| title_fullStr | Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity |
| title_full_unstemmed | Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity |
| title_short | Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity |
| title_sort | differences in plasma metabolites related to alzheimer s disease apoe ε4 status and ethnicity |
| topic | Alzheimer's disease APOE ε4 metabolite profile differences in Alzheimer's disease metabolomics multi‐ethnic plasma |
| url | https://doi.org/10.1002/trc2.12025 |
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