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Cited by 30Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Upregulation of Glycolytic Enzymes, Mitochondrial Dysfunction and Increased Cytotoxicity in Glial Cells Treated with Alzheimer’s Disease Plasma

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Jayasena, Tharusha, Poljak, Anne, Braidy, Nady, Smythe, George, Raftery, Mark, Hill, Mark, Brodaty, Henry, Trollor, Julian +2 more·2015·PLOS ONE
DOI 10.1371/journal.pone.0116092PMC PMC4364672
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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder associated with increased oxidative stress and neuroinflammation. Markers of increased protein, lipid and nucleic acid oxidation and reduced activities of antioxidant enzymes have been reported in AD plasma. Amyloid plaques in the AD brain elicit a range of reactive inflammatory responses including complement activation and acute phase reactions, which may also be reflected in plasma. Previous studies have shown that human AD plasma may be cytotoxic to cultured cells. We investigated the effect of pooled plasma (n = 20 each) from healthy controls, individuals with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) on cultured microglial cells. AD plasma and was found to significantly decrease cell viability and increase glycolytic flux in microglia compared to plasma from healthy controls. This effect was prevented by the heat inactivation of complement. Proteomic methods and isobaric tags (iTRAQ) found the expression level of complement and other acute phase proteins to be altered in MCI and AD plasma and an upregulation of key enzymes involved in the glycolysis pathway in cells exposed to AD plasma. Altered expression levels of acute phase reactants in AD plasma may alter the energy metabolism of glia.

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  • Elevated glycolysis has been viewed as a potential compensatory response to mitochondrial dysfunction after exposure to AD plasma, serving as an early indicator of cellular energy deficiency.

    “Elevated glycolysis has been viewed as a potential compensatory response to mitochondrial dysfunction after exposure to AD plasma, serving as an early indicator of cellular energy deficiency [26,27].”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [26]

    The Discussion (page unavailable) describes increased glycolysis after AD-plasma exposure as a possible compensation for compromised mitochondrial function, and the Results report impaired respiration alongside increased glycolysis in microglial cells. The paper does not identify elevated glycolysis as an early indicator of cellular energy deficiency; its separate reference to early events concerns mitochondrial dysfunction and altered energy metabolism in AD more broadly. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The authors' results support the increase in glycolytic enzymes observed in frontal cortex lysate of AD patients and in glial cells after treatment with AD plasma.

    “These results support the increase in glycolytic enzymes that has been observed in the frontal cortex lysate of AD patients as well as glial cells after treatment with AD plasma [25,26].”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [26]

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Cited by

Sorted by citations

Authors
Jayasena, T., Poljak, A., Braidy, N., Smythe, G., Raftery, M., Hill, M., Brodaty, H., Trollor, J., Kochan, N., & Sachdev, P.
Affiliations
UNSW Sydney (AU)
Corresponding author
Poljak, Anne
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-03-18
Volume
10
Issue
3
Pages
e0116092
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0116092
PMC
PMC4364672
OpenAlex
W2082832824
Cited by
30
References
4
Citations by year
2026: 4 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4
FWCI
2.00
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)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
  • UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Australian Government
  • Macquarie University
  • University of New South Wales
  • National Health and Medical Research Council (568969, 350833)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, microglia, glial cells, glycolytic enzymes, mitochondrial dysfunction, cytotoxicity, complement system, acute phase proteins, amnestic mild cognitive impairment, oxidative stress, neuroinflammation, energy metabolism
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cell Line, Transformed, Female, Glycolysis, Humans, Male, Mitochondria, Neuroglia, Plasma

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