Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment
Brain glucose hypometabolism is an early sign of Alzheimer’s disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/4/569 |
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| author | Angela J. Hanson William A. Banks Lisa F. Bettcher Robert Pepin Daniel Raftery Sandi L. Navarro Suzanne Craft |
| author_facet | Angela J. Hanson William A. Banks Lisa F. Bettcher Robert Pepin Daniel Raftery Sandi L. Navarro Suzanne Craft |
| author_sort | Angela J. Hanson |
| collection | DOAJ |
| description | Brain glucose hypometabolism is an early sign of Alzheimer’s disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a pilot study of older adults who underwent saline and triglyceride (TG) infusions. Older adults (12 cognitively normal (CN), age 65.3 ± 8.1, and 9 with cognitive impairment (CI), age 70.9 ± 8.6) underwent a 5 h TG or saline infusion on different days using a random crossover design; CSF was collected at the end of infusion. Aqueous metabolites were measured using a targeted mass spectroscopy (MS) platform focusing on 215 metabolites from over 35 different metabolic pathways. Data were analyzed using MetaboAnalyst 4.0 and SAS. Of the 215 targeted metabolites, 99 were detectable in CSF. Only one metabolite significantly differed by treatment: the ketone body 3-hydroxybutyrate (HBA). Post hoc analyses showed that HBA levels were associated with age and markers of metabolic syndrome and demonstrated different correlation patterns for the two treatments. When analyzed by cognitive diagnosis group, TG-induced increases in HBA were over 3 times higher for those with cognitive impairment (change score CN +9.8 uM ± 8.3, CI +32.4 ± 7.4, <i>p</i> = 0.0191). Interestingly, individuals with cognitive impairment had higher HBA levels after TG infusion than those with normal cognition. These results suggest that interventions that increase plasma ketones may lead to higher brain ketones in groups at risk for AD and should be confirmed in larger intervention studies. |
| first_indexed | 2024-03-11T04:45:07Z |
| format | Article |
| id | doaj.art-e5a770324cf447bb9fdd1471aa625b1a |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T04:45:07Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-e5a770324cf447bb9fdd1471aa625b1a2023-11-17T20:25:21ZengMDPI AGMetabolites2218-19892023-04-0113456910.3390/metabo13040569Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive ImpairmentAngela J. Hanson0William A. Banks1Lisa F. Bettcher2Robert Pepin3Daniel Raftery4Sandi L. Navarro5Suzanne Craft6Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USADivision of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98104, USADepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USADepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USADepartment of Anesthesiology and Pain Medicine, Northwest Metabolomics Research Center, University of Washington, Seattle, WA 98109, USADivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA 98109, USADepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27109, USABrain glucose hypometabolism is an early sign of Alzheimer’s disease (AD), and interventions which offset this deficit, such as ketogenic diets, show promise as AD therapeutics. Conversely, high-fat feeding may exacerbate AD risk. We analyzed the metabolomic profile of cerebrospinal fluid (CSF) in a pilot study of older adults who underwent saline and triglyceride (TG) infusions. Older adults (12 cognitively normal (CN), age 65.3 ± 8.1, and 9 with cognitive impairment (CI), age 70.9 ± 8.6) underwent a 5 h TG or saline infusion on different days using a random crossover design; CSF was collected at the end of infusion. Aqueous metabolites were measured using a targeted mass spectroscopy (MS) platform focusing on 215 metabolites from over 35 different metabolic pathways. Data were analyzed using MetaboAnalyst 4.0 and SAS. Of the 215 targeted metabolites, 99 were detectable in CSF. Only one metabolite significantly differed by treatment: the ketone body 3-hydroxybutyrate (HBA). Post hoc analyses showed that HBA levels were associated with age and markers of metabolic syndrome and demonstrated different correlation patterns for the two treatments. When analyzed by cognitive diagnosis group, TG-induced increases in HBA were over 3 times higher for those with cognitive impairment (change score CN +9.8 uM ± 8.3, CI +32.4 ± 7.4, <i>p</i> = 0.0191). Interestingly, individuals with cognitive impairment had higher HBA levels after TG infusion than those with normal cognition. These results suggest that interventions that increase plasma ketones may lead to higher brain ketones in groups at risk for AD and should be confirmed in larger intervention studies.https://www.mdpi.com/2218-1989/13/4/569metabolomicsketone bodiescerebrospinal fluidAlzheimer’sblood brain barrier |
| spellingShingle | Angela J. Hanson William A. Banks Lisa F. Bettcher Robert Pepin Daniel Raftery Sandi L. Navarro Suzanne Craft Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment Metabolites metabolomics ketone bodies cerebrospinal fluid Alzheimer’s blood brain barrier |
| title | Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment |
| title_full | Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment |
| title_fullStr | Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment |
| title_full_unstemmed | Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment |
| title_short | Cerebrospinal Fluid Metabolomics: Pilot Study of Using Metabolomics to Assess Diet and Metabolic Interventions in Alzheimer’s Disease and Mild Cognitive Impairment |
| title_sort | cerebrospinal fluid metabolomics pilot study of using metabolomics to assess diet and metabolic interventions in alzheimer s disease and mild cognitive impairment |
| topic | metabolomics ketone bodies cerebrospinal fluid Alzheimer’s blood brain barrier |
| url | https://www.mdpi.com/2218-1989/13/4/569 |
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