Amino acid catabolism in Alzheimer’s disease brain: Friend or foe?
Open accessAbstract
There is a dire need to discover new targets for Alzheimer's disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease.
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Neurons could use glucogenic or ketogenic amino acids to generate TCA intermediates to produce ATP through oxidative phosphorylation when glucose is scarce.
“Neurons could also use glucogenic or even ketogenic amino acids to generate TCA intermediates to produce ATP through oxidative phosphorylation when glucose is scarce [128].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [128]
Section 5 says that amino acid catabolism likely helps AD neurons maintain ATP when glucose metabolism declines, and Section 4.4 says branched-chain amino acid carbons can enter the citric acid cycle. The paper does not explicitly distinguish glucogenic from ketogenic amino acids in this pathway, and its discussion concerns impaired glucose metabolism in AD rather than glucose scarcity in neurons generally. Page numbers were not available in our copy. (LLM, conf=0.83)
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Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer’s Disease
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Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease
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Sex-specific DNA methylation differences in Alzheimer’s disease pathology
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- Authors
- Griffin, J. W. D., & Bradshaw, P. C.
- Affiliations
- East Tennessee State University (US)
- Corresponding author
- Bradshaw, Patrick C.
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2017-01
- Volume
- 2017
- Issue
- 1
- Pages
- 5472792-5472792
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC5316456
- OpenAlex
- W2584342410
- Cited by
- 185
- References
- 139
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 26 · 2023: 24 · 2022: 25 · 2021: 20 · 2020: 25 · 2019: 14 · 2018: 10 · 2017: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amino acid catabolism, amino acid oxidation, brain energy homeostasis, urea cycle, ammonia detoxification, endothelial cells, pathogenesis, therapeutic target
- MeSH terms
- Alzheimer Disease, Amino Acids, Animals, Brain, Homeostasis, Humans, Metabolism, Neurons
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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