Targeted metabolomic analysis in Parkinson’s disease brain frontal cortex and putamen with relation to cognitive impairment
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We performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson’s disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression. The affected pathways include neurotransmitters, bile acids, homocysteine metabolism, amino acids, TCA cycle, polyamines, β-alanine metabolism, fatty acids, acylcarnitines, ceramides, phosphatidylcholines, and several microbiome-derived metabolites. Previously reported levodopa-related homocysteine accumulation in cortex still best explains the dementia status in PD, which can be modified by dietary supplementation. Further investigation is needed to reveal the exact mechanisms behind this pathological change.
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Elevated levels of secondary bile acids are found in PD patients, while findings regarding primary bile acids have yielded varying results.
“Studies have revealed elevated levels of secondary BAs in PD patients, while findings regarding primary BAs have yielded varying results.377–380”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [377]
A reduction in glycine-conjugated primary bile acids, glycocholic acid and glycochenodeoxycholic acid, is reported in post-mortem frontal cortex samples of PD patients and is associated with duration of PD diagnosis.
“Conversely, a reduction in glycine-conjugated primary BAs (glycocholic acid and glycochenodeoxycholic acid) was reported in post-mortem frontal cortex samples of PD patients, which was associated with the duration of PD diagnosis.377”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [377]
Indoxyl sulfate is increased in Parkinson's disease patients and induces oxidative stress and inflammation in primary astrocytes and mixed glial cell cultures.
“On the other hand, the uremic toxin indoxyl sulfate is increased in PD patients.377,429 An elevated CSF/plasma ratio of indoxyl sulfate was detected in PD patients, with notably higher concentrations observed in patients experiencing motor fluctuations compared to those without motor fluctuations.429”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [377]
Aberrant glutamatergic neurotransmission is a key contributing factor to neurodegeneration and Parkinson's disease.
“Aberrant glutamatergic neurotransmission represents a key contributing factor to neurodegeneration and PD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [377]
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Flagged first, then by citations
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Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Kalecký, K., & Bottiglieri, T.
- Affiliations
- Baylor University (US)
- Baylor Scott & White Research Institute (US)
- Corresponding author
- Kalecký, Karel
- Venue
- npj Parkinson's Disease
- Published
- 2023-06-03
- Volume
- 9
- Issue
- 1
- Pages
- 84-84
- ISSN
- 2373-8057 (ISSN-L)
- PMC
- PMC10239505
- OpenAlex
- W4379206935
- Cited by
- 32
- References
- 102
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 11 · 2023: 2
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Parkinson s Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Aging Mind Foundation Dallas Barbara Wallace and Kelly King Charitable Foundation Trust Baylor Scott & White Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- Parkinson's disease, cognitive impairment, dementia, frontal cortex, putamen, brain metabolomics, homocysteine metabolism, levodopa, bile acids, acylcarnitines, ceramide, phosphatidylcholine, gut microbiota metabolites, TCA cycle, polyamines, disease progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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