Cited by 318Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

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Mitochondrial alterations in Alzheimer's disease

Baloyannis, Stavros J.·2006·Journal of Alzheimer s Disease

DOI 10.3233/jad-2006-9204

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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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Swerdlow, R. H., Koppel, S., Weidling, I., Hayley, C., Ji, Y., & Wilkins, H. M. (2017) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.12.017 · Cited by 106
“Overall mitochondrial size is reduced, although this is punctuated by the increased presence of overly swollen mitochondria with misshapen cristae [27, 63].”
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Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention
Peng, Y., Gao, P., Shi, L., Chen, L., Liu, J., & Long, J. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7763 · Cited by 110
“In early research, several groups observed different types of mitochondrial abnormalities in the brains or peripheral tissues of patients with AD and animal models (22, 157, 248, 270, 354, 419).”
Background
Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape
Salminen, A., Haapasalo, A., Kauppinen, A., Kaarniranta, K., Soininen, H. S., & Hiltunen, M. O. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.001 · Cited by 107
“…Impaired mito pathogenesis via disturbed epigenetic regulation of chromatin j.pneurobio.2015.05.001 conducted from post-mortem samples, have indicated that the number of mitochondria and the volume of mitochondrial space are reduced in affected neurons in AD (Hirai et al., 2001; Baloyannis, 2006).”
BackgroundInfluential
Hippocampal mitochondrial dysfunction in rat aging
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“For instance, patients with early to moderate Alzheimer’s disease have an 25% smaller hippocampal volume than healthy age-matched subjects (13, 24, 26) and show a postmortem marked ultrastructural damage in hippocampal mitochondria and neurons (4).”
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Quality Control in Neurons: Mitophagy and Other Selective Autophagy Mechanisms
Evans, C. S., & Holzbaur, E. L. F. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.06.031 · Cited by 109
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S-Nitrosylation of Critical Protein Thiols Mediates Protein Misfolding and Mitochondrial Dysfunction in Neurodegenerative Diseases
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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
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“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.”
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Adeli, H., & Ghosh‐Dastidar, S. (2010) · Thammasat University Digital Collections · Cited by 103
Mitochondria in Alzheimer's disease and their potential role in Alzheimer's proteostasis
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“Mitochondrial surface area decreases, while cristae structure is altered and increased variability in mitochondrial shape occurs (Baloyannis, 2006).”
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Methods 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 107
“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…”
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The ‘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 98
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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
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Disentangling Mitochondria in Alzheimer’s Disease
Johri, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111520 · Cited by 103
Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease
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Interaction between NH2-tau fragment and Aβ in Alzheimer's disease mitochondria contributes to the synaptic deterioration
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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).”
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Canonical Wnt signaling protects hippocampal neurons from Aβ oligomers: role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics
Silva-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 91
“Quantitative morphometric analysis of mitochondria shows increased abnormal and damaged mitochondria in the AD brain (Hirai et al., 2001; Baloyannis, 2006).”
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The 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
“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].”
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Shedding light on mitophagy in neurons: what is the evidence for PINK1/Parkin mitophagy in vivo?
Cummins, N., & Götz, J. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2692-9 · Cited by 88
Role of the mitochondrial sodium/calcium exchanger in neuronal physiology and in the pathogenesis of neurological diseases
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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).”
Background
Increased mtDNA mutations with aging promotes amyloid accumulation and brain atrophy in the APP/Ld transgenic mouse model of Alzheimer’s disease
Kukreja, L., Kujoth, G. C., Prolla, T. A., LEUVEN, F. V., & Vassar, R. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-16 · Cited by 85
“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].”
Background
Puerarin protects Alzheimer's disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways
Zhang, H., Liu, Y., Lao, M., Ma, Z., & Yi, X. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.09.013 · Cited by 86
AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons
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“, 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.”
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The mitochondrial hypothesis: Dysfunction, bioenergetic defects, and the metabolic link to Alzheimer's disease
Swerdlow, R. H. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.01.008 · Cited by 88
“Despite this, AD brains show more frequent enlargement of individual mitochondria with cristae disruption (Baloyannis, 2006).”
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Dendritic changes in visual pathways in glaucoma and other neurodegenerative conditions
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Endo-lysosomal pathway and ubiquitin-proteasome system dysfunction in Alzheimer's disease pathogenesis
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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].”
Background
The 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 88
Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities
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“Amongst these networks, research on mitochondrial dysfunction, known to be an early event in AD progression [121-123], should be emphasized.”
Background
Neurotoxic 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 84
“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
DOI: 10.3233/jad-2006-9204
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Mitochondrial alterations in Alzheimer's disease

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