Mitochondrial alterations in Alzheimer's disease
Abstract
Morphological alterations of mitochondria may be related to metabolic and energy deficiency in neurons in Alzheimer's disease and other neurodegenerative disorders. Mitochondrial dysfunction is also a hallmark of beta peptide induced neuronal toxicity in Alzheimer's disease. 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 the result is a cycle of increased mitochondrial dysfunction causing increased oxidative damage until the cellular energy supply falls below the threshold for cellular survival. In a series of studies on the morphological and morphometric estimation of mitochondria in Alzheimer's disease, by electron microscopy we noticed substantial morphological and morphometric changes in the neurons of the hippocampus, the acoustic cortex, the frontal cortex, the cerebellar cortex, the climbing fibers, the thalamus, the globus pallidus, the red nucleus and the locus coeruleus. The morphological alterations consisted of considerable changes of the mitochondrial cristae, accumulation of osmiophilic material, and decrease of their size, in comparison with the normal controls. Mitochondrial alterations were particularly prominent in neurons, which showed loss of dendritic spines and abbreviation of the dendritic arborization. The ultrastructural study of large number of neurons in the thalamus and the red nucleus revealed that the mitochondrial alterations did not coexist with cytoskeletal pathology and accumulation of amyloid deposits, though they were prominent in neurons, which demonstrated fragmentation of the cisternae of the Golgi apparatus. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship between the site and extent of mitochondrial abnormalities and the synaptic alterations suggests an intimate and early association between these features in Alzheimer's disease.
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Most studies report the number of intact, normal appearing mitochondria declines in AD brain.
“Most studies report the number of intact, normal appearing mitochondria declines [111, 138].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [138]
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MICOS and the mitochondrial inner membrane morphology – when things get out of shape
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“Additionally, electron-microscopic studies have described an increase in mitochondrial fragmentation in human AD brains (7, 131).”
The β2-Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis
Wills, L. P., Trager, R. E., Beeson, G. C., Lindsey, C. C., Peterson, Y. K., Beeson, C. C., & Schnellmann, R. G. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.191528 · Cited by 103 · see citing works
Novel Genetic Tools Reveal Cdk5's Major Role in Golgi Fragmentation in Alzheimer's Disease
Sun, K.-H., de Pablo, Y., Vincent, F., Johnson, E. O., Chavers, A. K., & Shah, K. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-11-1106 · Cited by 102 · see citing works
“Because Golgi fragmentation has been suggested to be an early event in AD pathology (Baloyannis, 2006), it supports our hypothesis that Golgi fragmentation alone may not be sufficient to cause acute toxicity.”
BackgroundResultAutomated EEG-Based Diagnosis of Neurological Disorders: Inventing the Future of Neurology
Adeli, H., & Ghosh‐Dastidar, S. (2010) · Thammasat University Digital Collections · Cited by 103 · see citing works
Mitochondria in Alzheimer's disease and their potential role in Alzheimer's proteostasis
Weidling, I. W., & Swerdlow, R. H. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113321 · Cited by 100 · see citing works
“Mitochondrial surface area decreases, while cristae structure is altered and increased variability in mitochondrial shape occurs (Baloyannis, 2006).”
BackgroundMethods for imaging mammalian mitochondrial morphology: A prospective on MitoGraph
Harwig, M. C., Viana, M. P., Egner, J. M., Harwig, J. J., Widlansky, M. E., Rafelski, S. M., & Hill, R. B. (2018) · Analytical Biochemistry · doi:10.1016/j.ab.2018.02.022 · Cited by 98 · see citing works
“In addition, changes in mitochondrial morphology occur in many human diseases including Alzheimer’s disease [28], amyotrophic lateral sclerosis [29], Parkinson’s disease [30–34], hypertrophic cardiomyopathy [35], and diabetes [36], however in many of these cases it is unclear whether the…”
BackgroundThe ‘mitochondrial contact site and cristae organising system’ (MICOS) in health and human disease
Eramo, M. J., Lisnyak, V., Formosa, L. E., & Ryan, M. T. (2019) · The Journal of Biochemistry · doi:10.1093/jb/mvz111 · Cited by 94 · see citing works
Dendritic pathology in Alzheimer's disease
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Amyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease
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OPA1 functionally interacts with MIC60 but is dispensable for crista junction formation
Barrera, M., Koob, S., Dikov, D., Vogel, F., & Reichert, A. S. (2016) · FEBS Letters · doi:10.1002/1873-3468.12384 · Cited by 94 · see citing works
“25 Baloyannis SJ (2006) Mitochondrial alterations in Alzheimer’s disease.”
BackgroundDisentangling Mitochondria in Alzheimer’s Disease
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“An impaired balance of fission/fusion and mitophagy toward enhanced fission (Wang et al., 2008) may also account for the mitochondrial morphological alterations found in several areas of AD patients (Baloyannis, 2006; Bubber et al., 2005; Wang et al., 2009).”
BackgroundSilva-Álvarez, C., Arrázola, M. S., Godoy, J. A., Ordenes, D., & Inestrosa, N. C. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00097 · Cited by 93 · see citing works
“Quantitative morphometric analysis of mitochondria shows increased abnormal and damaged mitochondria in the AD brain (Hirai et al., 2001; Baloyannis, 2006).”
BackgroundThe toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
“Abnormalities exist in mitochondrial fission/fusion and respiration protein levels in AD brain [120, 127], which may explain mitochondrial morphological alterations observed in several areas of AD patient brains [118] and apparent deficits in energy metabolism observed via PET scan [128].”
BackgroundShedding light on mitophagy in neurons: what is the evidence for PINK1/Parkin mitophagy in vivo?
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Can the emerging field of immunometabolism provide insights into neuroinflammation?
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Mitochondrial Abnormalities in Alzheimer’s Disease
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“Overall, the average size of AD neuron mitochondria is smaller than it is in control brain neurons (Baloyannis, 2006; Hirai et al., 2001).”
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“Aside from changes in mtDNA, AD mitochondria have decreased electron transport chain complex (ETC) IV, morphological changes in cristae, accumulation of osmiophilic material and decreased size [8,10].”
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AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons
Amadoro, G., Corsetti, V., Florenzano, F., Atlante, A., Ciotti, M. T., Mongiardi, M. P., Bussani, R., Nicolin, V., Nori, S. L., Campanella, M., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.10.018 · Cited by 85 · see citing works
“, 2012) as well as in human diseased specimens (Baloyannis, 2006; Chan, 2006; Hirai et al., 2001), due almost in part to an increased autophagic removal (Moreira et al.”
BackgroundInfluentialSwerdlow, R. H. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.01.008 · Cited by 85 · see citing works
“Despite this, AD brains show more frequent enlargement of individual mitochondria with cristae disruption (Baloyannis, 2006).”
BackgroundDendritic changes in visual pathways in glaucoma and other neurodegenerative conditions
Liu, M., Duggan, J., Salt, T. E., & Cordeiro, M. F. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.01.014 · Cited by 78 · see citing works
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“Previous studies indicated that mitochondrial dysfunction as one of early AD pathological features, including accumulation of dysfunctional mitochondria seen in cellular and animal models of AD and in brain tissue of AD patients [108–110], as well as defects in mitochondrial motility and dynamics [106,111,112].”
BackgroundThe Alzheimer’s Disease Mitochondrial Cascade Hypothesis: A Current Overview
Swerdlow, R. H. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221286 · Cited by 83 · see citing works
Pistollato, F., Ohayon, E. L., Lam, A., Langley, G. R., Novak, T. J., Pamies, D., Perry, G. L., Trushina, E. V., Williams, R. S. B., Roher, A. E., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9175 · Cited by 78 · see citing works
“Amongst these networks, research on mitochondrial dysfunction, known to be an early event in AD progression [121-123], should be emphasized.”
BackgroundNeurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons
Meng, X., Song, Q., Liu, Z., Liu, X., Wang, Y., & Liu, J. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1400544 · Cited by 78 · see citing works
“Preaggregated A β 42 inhibited the activity of isolated Complex IV, while monomeric A β did not exhibit toxicity (Crouch et al., 2005, 2006); this may be partially attributed to the presence of free Cu 2 + ions in cells.”
BackgroundInfluential
- Authors
- Baloyannis, S. J.
- Affiliations
- Department of Neurology, Aristotelian University, Thessaloniki 540 06, Greece
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2006-07-14
- Volume
- 9
- Issue
- 2
- Pages
- 119-126
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2120143950
- Cited by
- 318
- References
- 0
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 14 · 2021: 28 · 2020: 28 · 2019: 16 · 2018: 18 · 2017: 21 · 2016: 21 · 2015: 13 · 2014: 11 · 2013: 11 · 2012: 20
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (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, mitochondrial dysfunction
- MeSH terms
- Alzheimer Disease, Animals, Energy Metabolism, Homeostasis, Humans, Mitochondria, Oxidative Stress
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