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Cited by 131Mitochondrial Function and PathologyAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles

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Sonntag, Kai-C., Ryu, Woo-In, Amirault, Kristopher M., Healy, Ryan A., Siegel, Arthur J., McPhie, Donna L., Forester, Brent, Cohen, Bruce M.·2017·Scientific Reports
DOI 10.1038/s41598-017-14420-xPMC PMC5656579
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Abstract

Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal aging and disturbed bioenergetics may be an important contributing mechanism underlying late-onset Alzheimer’s disease (LOAD). We investigated the bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as a function of age and disease. LOAD cells exhibited an impaired mitochondrial metabolic potential and an abnormal redox potential, associated with reduced nicotinamide adenine dinucleotide metabolism and altered citric acid cycle activity, but not with disease-specific changes in mitochondrial mass, production of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD fibroblasts demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to IGF-1. The increase of glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to be inherent, as they were disease- and not age-specific. Our findings support the hypothesis that impairment in multiple interacting components of bioenergetic metabolism may be a key mechanism contributing to the risk and pathophysiology of LOAD.

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  • Some studies found that APOE4 reduced glycolysis, whereas others observed a shift from oxidative to glycolytic metabolism in APOE4 cells with higher glycolytic activity in APOE4 than APOE3.

    “Some studies found that APOE4 reduced glycolysis [28,39], whereas others observed a shift from oxidative to glycolytic metabolism in APOE4 cells with higher glycolytic activity in APOE4 than APOE3 [40,41,42].”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [42]

    The Results (Bioenergetics Parameters Related to Energy Production and Glycolysis; page unavailable) report evidence of a shift from oxidative phosphorylation toward glycolysis in late-onset Alzheimer’s disease fibroblasts, with elevated lactate relative to controls. The paper does not establish that this shift occurs specifically in APOE4 cells or that their glycolytic activity exceeds that of APOE3 cells. (LLM, conf=0.87)

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  • Many contradictory results on the impact of APOE on energy metabolism have been published.

    “In general, many contradictory results on the impact of APOE on energy metabolism have been published.”

    From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [42]

    The Discussion (page unavailable) says Apoε4 has been implicated in damaging the oxidative system, but does not say that published findings on APOE and energy metabolism are contradictory. Searches for contradictory or inconsistent APOE findings found no passage addressing that point. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Sonntag, K.-C., Ryu, W.-I., Amirault, K. M., Healy, R. A., Siegel, A. J., McPhie, D. L., Forester, B., & Cohen, B. M.
Affiliations
Harvard University (US)
Corresponding author
Sonntag, Kai-C.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-10-25
Volume
7
Issue
1
Pages
14038-14038
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-14420-x
PMC
PMC5656579
OpenAlex
W2766930070
Cited by
131
References
5
Citations by year
2026: 4 · 2025: 13 · 2024: 15 · 2023: 16 · 2022: 19 · 2021: 28 · 2020: 15 · 2019: 15 · 2018: 6
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
McLean Hospital
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
late-onset Alzheimer's disease, bioenergetics, energy metabolism, fibroblasts, redox potential, NAD+ metabolism, TCA cycle, glycolysis, insulin-like growth factor I, glucose uptake, normal aging, mitochondrial dysfunction
MeSH terms
Age Factors, Alzheimer Disease, Energy Metabolism, Fibroblasts, Glycolysis, Humans, Mitochondria, Oxidation-Reduction, Reactive Oxygen Species

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