Energy metabolism, oxidative stress and neuronal degeneration in Alzheimer’s disease
Abstract
Both altered energy metabolism and oxidative stress have been proposed to contribute to tissue damage in neurogenerative diseases. Animal models and cell culture studies provide evidence for a role of these processes in several forms of neuronal death. Reductions in the activities of some key mitochondrial enzymes have been found in autopsied brain in Alzheimer's disease. However, results obtained with biopsied brain tissue as well as assessments of metabolic rates for glucose in vivo indicate that a reduced functional capacity of mitochondria is probably not a general feature in the brain in Alzheimer's disease. These studies do not address the possibility that short-lived changes in energy metabolism affecting a small number of cells at any one time could be contributing to cell death. Several findings point to a moderate increase in oxidative damage in those areas of brain which are most severely affected in this disease, probably resulting from an increase in production of reactive oxygen species. Whether this is a contributor to neurodegeneration or a consequence of it remains unresolved.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oxidative stress associated with Aβ pathology plays an important role in the death of neurons in the AD brain.
“Oxidative stress associated with Aβ pathology plays an important role in the death of neurons in the AD brain [82,83,84,85].”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [85]
Cited by
Sorted by citations
Devi, L., Prabhu, B. M., Galati, D. F., Avadhani, N. G., & Anandatheerthavarada, H. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1469-06.2006 · Cited by 792 · see citing works
“Mitochondrial dysfunction may play a role in the degeneration/cell death of neurons during the pathogenesis of AD (Sims, 1996; Zhu et al., 2004).”
BackgroundAnandatheerthavarada, H. K., Biswas, G., Robin, M.-A., & Avadhani, N. G. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200207030 · Cited by 571 · see citing works
“A general change in glucose utilization, increased oxidative stress, and Ca(2) deregulation are additional metabolic defects in the AD brain that may also be associated with defective mitochondrial function (Sims, 1996; Beal, 1998).”
BackgroundInfluentialButterfield, D. A., Reed, T., Newman, S. F., & Sultana, R. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.05.037 · Cited by 564 · see citing works
“Decreased α-ketoglutarate dehydrogenase activity in the parietal and temporal cortex of AD patients has also been reported, which could be related to the HNE binding to α-ketoglutarate [126–130], though this could be affected by longer postmortem intervals [131].”
BackgroundBastianetto, S., Zheng, W., & Quirion, R. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703626 · Cited by 302 · see citing works
“Because free radicals are able to alter the activity of mitochondrial enzymes that are involved in MTT reduction (Sims, 1996), we also used Neutral Red, a dye which is taken up by lysosomes of living cells, as an additional marker of hippocampal cell integrity (Bastianetto et al., 2000).”
MethodDehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage
Bastianetto, S., Ramassamy, C., Poirier, J., & Quirion, R. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00002-9 · Cited by 257 · see citing works
Jiang, D., Men, L., Wang, J., Zhang, Y., Chickenyen, S., Wang, Y., & Zhou, F. (2007) · Biochemistry · doi:10.1021/bi700508n · Cited by 202 · see citing works
“Together with these pathological characteristics, intracellular lesions, including impairment of mitochondrial energy metabolism, have also been purported to be a cause of the AD development (9, 10, 16, 17).”
BackgroundDragicevic, N., Smith, A., Lin, X., Yuan, F., Copes, N., Delic, V., Tan, J., Cao, C., Shytle, R. D., & Bradshaw, P. C. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101629 · Cited by 189 · see citing works
“Mitochondrial dysfunction, apoptosis, and disruption of Ca2+ homeostasis are pathophysiological processes known to occur in AD brain [23–29].”
Dragicevic, N., Copes, N., O’Neal-Moffitt, G., Jin, J., Buzzeo, R. W., Mamcarz, M., Tan, J., Cao, C., Olcese, J., Arendash, G. W., et al. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00864.x · Cited by 185 · see citing works
Devi, L., & Anandatheerthavarada, H. K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.007 · Cited by 150 · see citing works
Lees, G. J. (2000) · Drugs · doi:10.2165/00003495-200059010-00004 · Cited by 138 · see citing works
Neuroprotective therapeutics for Alzheimer's disease: progress and prospects
Palmer, A. M. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.12.007 · Cited by 133 · see citing works
Mitochondrial aging and dysfunction in Alzheimer's disease
Sullivan, P. G., & Brown, M. R. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.12.007 · Cited by 113 · see citing works
Wang, X., Ou, D., Yin, J., Wu, G., & Wang, J. (2009) · Amino Acids · doi:10.1007/s00726-009-0242-y · Cited by 111 · see citing works
“metabolism, which undergoes marked changes in response to stress ( Sims 1996; Wu et al. 2007, 2008b).”
BackgroundAmyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease
Anandatheerthavarada, H. K., & Devi, L. (2007) · The Neuroscientist · doi:10.1177/1073858407303536 · Cited by 95 · see citing works
Palmer, A. M. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050161 · Cited by 92 · see citing works
Land, S. C., Porterfield, D. M., Sanger, R. H., et al. (1999) · Journal of Experimental Biology · doi:10.1242/jeb.202.2.211 · Cited by 91 · see citing works
Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice
Matthews, D. G., Caruso, M., Murchison, C. F., Zhu, J. Y., Wright, K. M., Harris, C. J., Gray, N. E., Quinn, J. F., & Soumyanath, A. (2019) · Antioxidants · doi:10.3390/antiox8120630 · Cited by 86 · see citing works
Studzinski, C. M., MacKay, W. A., Beckett, T. L., Henderson, S. T., Murphy, M. P., Sullivan, P. G., & Burnham, W. M. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.005 · Cited by 82 · see citing works
Yotter, R. A., & Wilson, D. M. (2004) · IEEE Sensors Journal · doi:10.1109/jsen.2004.830954 · Cited by 76 · see citing works
Adlard, P. A., West, A. K., & Vickers, J. C. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0203 · Cited by 71 · see citing works
Lapchak, P. A. (2011) · Expert Review of Medical Devices · doi:10.1586/erd.11.64 · Cited by 71 · see citing works
Torroja, L., Ortuño‐Sahagún, D., Ferrús, A., Hämmerle, B., & Barbas, J. A. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.1009 · Cited by 68 · see citing works
“Defects in mitochondrial function have been reported in AD, and it has been proposed that mitochondrial dysfunction is a primary causal factor for AD (Sims, 1996).”
BackgroundWebster, M.-T., Pearce, B. R., Bowen, D. M., & Francis, P. T. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050098 · Cited by 62 · see citing works
“However, it is difficult in these studies to completely rule out effects from post mortem degradation or altered agonal state, especially where the brain is already affected by disease (Sims et al., 1987a; Francis et al., 1993; Sims, 1996).”
BackgroundInfluentialMacPherson, R. E. K., Baumeister, P., Peppler, W. T., Wright, D. C., & Little, J. P. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00299.2015 · Cited by 58 · see citing works
Law, A., Gauthier, S. G., & Quirion, R. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704179 · Cited by 43 · see citing works
“Since free radicals have been shown to alter the activities of mitochondrial enzymes (Sims, 1996), NR, a dye which is taken up by lysosomes of living cells (Bastianetto et al., 1999), was also used as an additional cellular integrity marker in some experiments to con®rm the results obtained with…”
MethodReview: The renin-angiotensin-aldosterone system and Alzheimer's disease?
Kehoe, P. G. (2003) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.3317/jraas.2003.017 · Cited by 40 · see citing works
“Reduced energy metabolism has been identified to be another prominent feature in AD (reviewed by Sims).(100) In part, this is largely contributed to by ageassociated increased disruption to mitochondrial function, which can result initially from the formation of damaging free radicals, that in turn cause further mitoc…”
BackgroundPająk, B., Kania, E., & Orzechowski, A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1805304 · Cited by 29 · see citing works
“Due to their limited glycolytic capacity (lack of salvage pathway), neurons are highly dependent on mitochondrial function for energy release and severely affected by the limited oxygen and glucose supply, making them especially susceptible to energy dyshomeostasis [29].”
BackgroundAnandatheerthavarada, H. K., & Devi, L. (2007) · Reviews in the Neurosciences · doi:10.1515/revneuro.2007.18.5.343 · Cited by 28 · see citing works
Acute exercise and brain BACE 1 protein content: a time course study
Yang, A. J. T., Hayward, G. C., & MacPherson, R. E. K. (2019) · Physiological Reports · doi:10.14814/phy2.14084 · Cited by 26 · see citing works
“The exact mechanisms leading to changes in BACE1 protein content are multifaceted, however increased cellular stress and impairments in energy metabolism represent early abnormalities that precede or accompany the initial stages of cognitive impairment (Sims 1996; Steen et al. 2005).”
BackgroundLCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments
Guo, C., Li, W., Liu, Y., Mahaman, Y. A. R., Wang, J., Liu, R., Li, S., & Wang, X. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07469-4 · Cited by 24 · see citing works
“Mitochondrial damage, in turn, can exert adverse biological effects on tissues and cells by activating intracellular signal transduction pathways, leading to the upregulation of cytokines and ROS (oxidative stress) [58, 59].”
Farimani, M. M., Sarvestani, N. N., Ansari, N., et al. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200420a · Cited by 22 · see citing works
The Systemic Theory of Living Systems and Relevance to CAM: the Theory (Part III)
Rangel, J. A. O. (2005) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/neh119 · Cited by 22 · see citing works
Stobadine: Bellwether of a broader view of drug actions
Vincenzi, F. F., & Hinds, T. R. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00438-5 · Cited by 9 · see citing works
7α-Hydroperoxycholesterol causes CNS neuronal cell death
Kölsch, H., Ludwig, M. Z., Lütjohann, D., et al. (2000) · Neurochemistry International · doi:10.1016/s0197-0186(99)00157-6 · Cited by 8 · see citing works
The Use of the Mitochondrial Toxin 3-NP to Uncover Cellular Dysfunction in Huntington’s Disease
Hernández, E., la Rosa-Lpez, G. D., & Mendoza, E. (2012) · InTech eBooks · doi:10.5772/31284 · Cited by 6 · see citing works
Abdollahian, N. P., Cada, A. M., Gonzalez-Lima, F., & de la Torre, J. C. (1998) · Springer eBooks · doi:10.1007/978-1-4757-9936-1_9 · Cited by 7 · see citing works
Emrani, S., Zhiani, R., & Dolatabadi, S. (2015) · The Neuroscience Journal of Shefaye Khatam · doi:10.18869/acadpub.shefa.3.3.27 · Cited by 4 · see citing works
Abrak, S. B., & Zhiani, R. (2014) · The Neuroscience Journal of Shefaye Khatam · doi:10.18869/acadpub.shefa.2.1.31 · Cited by 2 · see citing works
ROLE OF CALCIUM AND NITRIC OXIDE SYNTHASE (NOS) IN BRAIN MITOCHONDRIAL DYSFUNCTION
Nukala, V. N. (2007) · UKnowledge (University of Kentucky) · Cited by 1 · see citing works
Afferent Regulation of Developmental Fate in the Songbird Telencephalon
Johnson, F. (2007) · Springer eBooks · doi:10.1007/978-0-585-29598-5_10 · Cited by 1 · see citing works
Flavonoids in Transgenic Alzheimer's Disease Mouse Models
Sabogal-Guáqueta, A. M., Osorio, E., & Cardona-Gómez, G. P. (2017) · doi:10.1002/9781119155195.ch2 · Cited by 2 · see citing works
Pathogenesis of Alzheimer Disease: Metabolic Factors
(2004) · Springer eBooks · doi:10.1007/0-306-48529-x_15
Hyperpolarized NMR study of the impact of alzheimer’s disease on diabetes using a novel rat model
Rehman, U., Datta, K., Liu, S.-C., Park, J. M., Sriram, R., Hong, D., Chen, Q., Mori, H., Trinh, V., Berman, R. F., et al. (2026) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-026-01231-w
“Whether the T2D brain has an insufficient amount of insulin reaching the cerebrospinal fluid (CSF) or suffers from insulin resistance poses a critical question in physiology [2, 4, 5, 44, 45].”
Newman, S. F. (2009) · UKnowledge (University of Kentucky)
- Authors
- Sims, N. R.
- Affiliations
- Flinders University (AU)
- Corresponding author
- Sims, Neil R.
- ORCID
- Sims, Neil R.
- Venue
- Neurodegeneration
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 5
- Issue
- 4
- Pages
- 435-440
- ISSN
- 1055-8330 (ISSN-L)
- OpenAlex
- W1999483875
- Cited by
- 45
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2019: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurodegeneration (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, energy metabolism, oxidative stress, neurodegeneration, mitochondrial dysfunction, reactive oxygen species, glucose metabolism, mitochondrial enzymes
- MeSH terms
- Alzheimer Disease, Energy Metabolism, Humans, Nerve Degeneration, Neurons, Oxidative Stress
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 ›
Are you an author, or do you see a problem with this page? Request a review
