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Cited by 438Dementia and Cognitive Impairment ResearchMetabolomics and Mass Spectrometry StudiesAlzheimer's disease research and treatments

Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using Metabolomics

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Trushina, Eugenia, Dutta, Tumpa, Persson, Xuan-Mai T., Mielke, Michelle M., Petersen, Ronald C.·2013·PLoS ONE
DOI 10.1371/journal.pone.0063644PMC PMC3658985
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Abstract

Alzheimer's Disease (AD) currently affects more than 5 million Americans, with numbers expected to grow dramatically as the population ages. The pathophysiological changes in AD patients begin decades before the onset of dementia, highlighting the urgent need for the development of early diagnostic methods. Compelling data demonstrate that increased levels of amyloid-beta compromise multiple cellular pathways; thus, the investigation of changes in various cellular networks is essential to advance our understanding of early disease mechanisms and to identify novel therapeutic targets. We applied a liquid chromatography/mass spectrometry-based non-targeted metabolomics approach to determine global metabolic changes in plasma and cerebrospinal fluid (CSF) from the same individuals with different AD severity. Metabolic profiling detected a total of significantly altered 342 plasma and 351 CSF metabolites, of which 22% were identified. Based on the changes of >150 metabolites, we found 23 altered canonical pathways in plasma and 20 in CSF in mild cognitive impairment (MCI) vs. cognitively normal (CN) individuals with a false discovery rate <0.05. The number of affected pathways increased with disease severity in both fluids. Lysine metabolism in plasma and the Krebs cycle in CSF were significantly affected in MCI vs. CN. Cholesterol and sphingolipids transport was altered in both CSF and plasma of AD vs. CN. Other 30 canonical pathways significantly disturbed in MCI and AD patients included energy metabolism, Krebs cycle, mitochondrial function, neurotransmitter and amino acid metabolism, and lipid biosynthesis. Pathways in plasma that discriminated between all groups included polyamine, lysine, tryptophan metabolism, and aminoacyl-tRNA biosynthesis; and in CSF involved cortisone and prostaglandin 2 biosynthesis and metabolism. Our data suggest metabolomics could advance our understanding of the early disease mechanisms shared in progression from CN to MCI and to AD.

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  • Proteomic approaches have revealed dysregulation in synaptic proteins, immune modulators, and metabolic enzymes that extend beyond the classical amyloid and tau pathways.

    “These approaches have revealed dysregulation in synaptic proteins, immune modulators, and metabolic enzymes that extend beyond the classical amyloid and tau pathways134,160,170, 171, 172, 173.”

    From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [170]

    The Results (page unavailable) report altered neurotransmitter and metabolic pathways in plasma and CSF, supporting the broader point that changes extend beyond amyloid and tau. But the Introduction identifies the approach as metabolomics, and the reported measurements are metabolites; this paper does not establish dysregulation of synaptic proteins, immune modulators, or metabolic enzymes through proteomic analysis. (LLM, conf=0.86)

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Authors
Trushina, E., Dutta, T., Persson, X.-M. T., Mielke, M. M., & Petersen, R. C.
Affiliations
Mayo Clinic (US)
Corresponding author
Trushina, Eugenia
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-05-20
Volume
8
Issue
5
Pages
e63644
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0063644
PMC
PMC3658985
OpenAlex
W2159671087
Cited by
438
References
8
Citations by year
2026: 24 · 2025: 38 · 2024: 27 · 2023: 30 · 2022: 21 · 2021: 47 · 2020: 38 · 2019: 34 · 2018: 43 · 2017: 34 · 2016: 28 · 2015: 36 · 2014: 30 · 2013: 8
FWCI
24.17
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (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, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Mayo Clinic
  • National Institute on Aging (AG016574, U01AG006786, AG-006786, P50AG016574)
  • National Institute of Environmental Health Sciences (R01ES020715)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, mild cognitive impairment, plasma metabolites, cerebrospinal fluid metabolites, metabolic pathways, lysine metabolism, TCA cycle, cholesterol transport, sphingolipid transport, energy metabolism, mitochondrial function, aminoacyl-tRNA biosynthesis, tryptophan metabolism, polyamine metabolism, amyloid-beta, early diagnosis, disease severity
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Multivariate Analysis, Case-Control Studies, Principal Component Analysis, Metabolic Networks and Pathways, Metabolomics, Metabolome, Cognitive Dysfunction

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