Targeted metabolomic analysis of nitric oxide/L-arginine pathway metabolites in dementia: Association with pathology, severity, and structural brain changes
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L-Arginine/NO pathway is altered in Alzheimer disease (AD). Its clinical relevance and pathway status in vascular dementia (VaD) are unknown. Using targeted metabolomics (a liquid chromatography-mass spectrometry) we assessed L-arginine, L-citrulline, dimethylamine (DMA), asymmetric dimethyl arginine (ADMA) and symmetric dimethylarginine (SDMA) in AD (n = 48), mixed-type dementia (MD; n = 34), VaD (n = 40) and non-demented individuals (n = 140) and determined their clinical relevance (the association with dementia pathology, cognitive impairment, and structural brain damage). L-Arginine, ADMA, L-arginine/ADMA, and L-citrulline levels were decreased in dementia and L-arginine, L-citrulline, age and sex were its independent predictors correctly classifying 91% of cases. L-Arginine and L-arginine/ADMA were differentiating between VaD and AD with moderate accuracy. L-Arginine, L-arginine/ADMA, SDMA, and DMA reflected structural brain changes. DMA and L-citrulline were elevated in patients with strategic infarcts and SDMA, L-arginine/ADMA, and DMA were independent predictors of Hachinski ischemic score. ADMA and SDMA accumulation reflected severity of cognitive impairment. In summary, L-Arginine/NO pathway is altered in neurodegenerative and vascular dementia in association with neurodegenerative and vascular markers of brain damage and severity of cognitive impairment.
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Untargeted and targeted metabolomics studies indicate that the L-arginine/nitric oxide pathway is altered in Alzheimer's disease.
“Untargeted and targeted metabolomics studies have indicated that L-arginine/nitric oxide (NO) pathway is altered in AD [35,36].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [35]
Untargeted and targeted metabolomics studies have indicated that L-arginine/NO pathway is altered in AD.
“Untargeted and targeted metabolomics studies have indicated that L-arginine/NO pathway is altered in AD [35,36].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [35]
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- Authors
- Fleszar, M. G., Wiśniewski, J., Zboch, M., Diakowska, D., Gamian, A., & Krzystek-Korpacka, M.
- Affiliations
- Wroclaw Medical University (PL)
- Venue
- Scientific Reports
- Published
- 2019-09-24
- Volume
- 9
- Issue
- 1
- Pages
- 13764-13764
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6760237
- OpenAlex
- W2976246130
- Cited by
- 80
- References
- 66
- Citations by year
- 2026: 13 · 2025: 10 · 2024: 9 · 2023: 15 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 1
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu (#ST-882)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- Alzheimer's disease, vascular dementia, L-arginine, citrulline, asymmetric dimethylarginine, symmetric dimethylarginine, dimethylamine, dementia biomarkers, cognitive impairment severity, cerebral infarction, Hachinski Ischemic Score, structural brain damage, dementia classification
- MeSH terms
- Arginine, Brain, Citrulline, Dementia, Female, Humans, Male, Middle Aged, Nitric Oxide, Signal Transduction, Biomarkers, Metabolomics
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