Cited by 562Alzheimer's disease research and treatmentsMitochondrial Function and PathologyDementia and Cognitive Impairment Research

The DOI matches its Crossref record; 145 of the 145 references it cites were found in a registry or an index.

The Alzheimer’s Disease Mitochondrial Cascade Hypothesis

Open access

Swerdlow, Russell H., Burns, Jeffrey M., Khan, Shaharyar M.·2010·Journal of Alzheimer s Disease

DOI 10.3233/jad-2010-100339PMC PMC2883665

Open this paper in CoChat — free account Open PDF

Abstract

We first proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD) in 2004. Our core assumptions were a person's genes determine baseline mitochondrial function and durability, this durability determines how mitochondria change with advancing age, and critical changes in mitochondrial function initiate other pathologies characteristic of AD. Since then several lines of investigation report data consistent with or supportive of our hypothesis. In particular, AD endophenotype studies suggest a strong maternal genetic contribution, and links between mitochondrial function, tau phosphorylation, and amyloid-beta (Abeta) amyloidosis are increasingly recognized. As predicted, AD therapies designed to reduce Abeta thus far have had at best very limited clinical benefits; our hypothesis identifies alternative therapeutic targets. While placing mitochondria at the apex of an AD cascade certainly remains controversial, it is increasingly accepted by the AD research community that mitochondria play an important role in the late-onset forms of the disease. Even if the mitochondrial cascade hypothesis proves incorrect, considering its assumptions could potentially advance our understanding of sporadic, late-onset AD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3233/jad-2010-100339

Cites

145 of 145 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · cited 1×
“basis of this relationship remains uncertain [99].”
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · cited 1×
“For almost twenty years the amyloid cascade hypothesis has dominated Alzheimer’s disease (AD) thinking, modeling, and therapeutic development efforts [1].”
Background
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · cited 1×
“The amyloid cascade hypothesis was formulated after an AβPP mutation was reported in a family with autosomal dominant amyloid angiopathy, dementia, and AD-typical histology [4].”
Background
Alzheimer’s disease
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · cited 1×
“Two other genes, presenilin 1 and 2, also contain mutations in autosomal dominant AD and the presenilin proteins are reportedly part of the gamma secretase complex that processes APP [5,6,7,8].”
Background
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734 · cited 3×
“This has led some investigators to speculate somatic mtDNA mutation contributes to age-related declines in mitochondrial function, and available data support this view [38, 50].”
BackgroundResult
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · cited 1×
“In autosomal dominant AD, mutations in each of these proteins are believed to shift APP processing towards Aβ42 [9].”
Background
Candidate gene for the chromosome 1 familial Alzheimer’s disease locus
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., et al. (1995) · Science · doi:10.1126/science.7638622 · Cited by 2,577

Flagged first, then by citations

Show all 145 references

Research works printed but not linked: 4

[111]Johnson DK Wilkins CH Morris JC Accelerated Weight Loss May Precede Diagnosis in Alzheimer Disease Arch Neurol 2006 63 1312 1317 16966511
[112]Stewart R Masaki K Xue QL Peila R Petrovitch H White LR Launer LJ A 32-Year Prospective Study of Change in Body Weight and Incident Dementia: The Honolulu-Asia Aging Study Archives of Neurology 2005 62 55 60 15642850
[113]BarrettConnor E Edelstein SL CoreyBloom J Wiederholt WC Weight loss precedes dementia in community-dwelling older adults Journal of the American Geriatrics Society 1996 44 1147 1152 8855991
[114]White H Pieper C Schmader K Fillenbaum G Weight change in Alzheimer's disease J Am Geriatr Soc 1996 44 265 272 8600194

Sorted by citations

Items 401–500 of 562

Medium-chain fatty acids in nutritional therapy: A review
Zulkanain, I. N., Rahim, S. A., Camalxaman, S. N., & Mazlan, M. (2020) · Malaysian Journal of Fundamental and Applied Sciences · doi:10.11113/mjfas.v16n3.1610 · Cited by 7
“AD and T2D are closely associated whereby, people with T2D have a higher chance to develop AD [44].”
Background
Willin/FRMD6 Mediates Mitochondrial Dysfunction Relevant to Neuronal Aβ Toxicity
Chen, D., Yu, W., Aitken, L., & Gunn‐Moore, F. J. (2022) · Cells · doi:10.3390/cells11193140 · Cited by 7
Misfolded proteins as a therapeutic target in Alzheimer's disease
Liyanage, S. I., & Weaver, D. F. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.08.003 · Cited by 8
Identification of Structural Calcium Binding Sites in Membrane-Bound Presenilin 1 and 2
Mehra, R., & Kepp, K. P. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c01712 · Cited by 7
Role of mitochondria in neuronal function and survival in the enteric and central nervous systems
KURAL, İ., Mombeek, L. M. M., & Wilson, D. M. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06053-5 · Cited by 8
“These mitochondrial alterations then accelerate Aβ and Tau pathology, ultimately driving neurode - generation [156].”
Targeting the microbiota-mitochondria crosstalk in neurodegeneration with senotherapeutics
Homolak, J. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.02.018 · Cited by 8
Dysfunctional energy and future perspective of low dose H2O2 as protective agent in neurodegenerative disease
Widyarti, S., Wibowo, S., Sabarudin, A., Abhirama, I., & Sumitro, S. B. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18123 · Cited by 6
A Metabolomics Analysis of a Novel Phenotype of Older Adults at Higher Risk of Dementia
Sultana, M., Camicioli, R. M., Dixon, R. A., Whitehead, S. N., Pieruccini‐Faria, F., Petrotchenko, E. V., Speechley, M. R., Borchers, C. H., & Montero‐Odasso, M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230683 · Cited by 6
Pluripotent Stem Cells for Uncovering the Role of Mitochondria in Human Brain Function and Dysfunction
Zink, A., Priller, J., & Prigione, A. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.02.005 · Cited by 6
“In AD, mitochondrial dysfunction appears to precede Aβ deposition (Moreira et al., 2010; Swerdlow et al., 2010).”
Background
Correction of mitochondrial dysfunction with trimethoxy-substituted monocarbonyl curcumin analogues in experimental Alzheimer’s disease
Pozdnyakov, D. I., Vikhor, A. A., Руковицина, В. М., & Тоникович, О. Э. (2024) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2023-11-6-471-481 · Cited by 7
Backwaters and rapids on the amyloid river
Burns, J. M., & Swerdlow, R. H. (2013) · Neurology · doi:10.1212/wnl.0b013e3182840d14 · Cited by 5
“It is also important to consider, however, that if amyloid turns out to be only a secondary biomarker of the disease, as opposed to its cause, then targeting its accumulation at any stage will have, at most, a limited effect on clinical outcomes.(7) Finally, the fibrillar deposition of amyloid in the brain parenchyma…”
BackgroundSelf-citation
Deciphering Early and Progressive Molecular Signatures in Alzheimer’s Disease through Integrated Longitudinal Proteomic and Pathway Analysis in a Rodent Model
Yadikar, H., Ansari, M. A., Abu‐Farha, M., Joseph, S., Thomas, B. T., & Al‐Mulla, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126469 · Cited by 5
“These findings echo the mitochondrial cascade hypothesis [46], which posits mitochondrial dysfunction as a primary event leading to AD.”
Background
Gut microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease
Al-Abbas, N. S., & Shaer, N. A. (2024) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823241309024 · Cited by 5
“82 Targeting metabolic pathways involving succinate has emerged as a potential therapeutic strategy for neurodegenerative diseases.”
The Supramolecular Architecture of Mitochondrial Complex I in the Rat Brain Is Altered by Alzheimer's‐Like Cerebral Amyloidosis
Novack, G. V., Galeano, P., Defelipe, L. A., Campanelli, L., Campuzano, K. S., Rotondaro, C., Castaño, E. M., Carmo, S. D., Cuello, A. C., García-Alai, M., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70017 · Cited by 5
“(Swerdlow et al. 2010; Moreira et al. 2010; Tillement et al. 2011; Manczak et al. 2006; Cha et al. 2012; Reddy et al. 2010).”
Mitochondria and Alzheimer’s Disease
Balogiannis, S. (2014) · Journal of Neurology & Stroke · doi:10.15406/jnsk.2014.01.00028 · Cited by 4
“On the basis of the substantial role that mitochondrial pathology [83] and mitochondrial genetic defects [84-87] seems to play in the pathogenetic cascade of AD [15,88] new strategies inducing protection to mitochondria by inhibition of mitochondrial β-oxidation [89-92], inhibition of ERK-DLP1 signaling and mitochondr…”
Background
A UPLC-Q-TOF/MS-Based Metabolomics Study on the Effect of Corallodiscus flabellatus (Craib) B. L. Burtt Extract on Alzheimer’s Disease
Wang, Y., Zhou, N., Si, Y., Bai, Z., Li, M., Feng, W., & Zheng, X. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/8868690 · Cited by 5
Mitochondrial DNA and Alzheimer’s disease: a first case–control study of the Tunisian population
Salem, N. B., Boussetta, S., de Rojas, I., Moreno–Grau, S., Montrreal, L., Mokni, N., Mahmoud, I., Younes, S., Daouassi, N., Frih-Ayed, M., et al. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06978-7 · Cited by 5
A comparison of mtDNA deletion mutant proliferation mechanisms
Holt, A. G., & Davies, A. M. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111244 · Cited by 5
Eight weeks of creatine monohydrate supplementation is associated with increased muscle strength and size in Alzheimer’s disease: data from a single-arm pilot study
Smith, A. N., Sullivan, D. K., Morris, J. K., Carbuhn, A. F., Herda, T. J., & Taylor, M. K. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1670641 · Cited by 6
“Modest gains in muscle size can improve functional capacity (34) and glucose metabolism (35), which is perturbed in AD (36).”
Fluorescence lifetime imaging ophthalmoscopy adds the retina to cortical pathology for visual dysfunction in neurodegenerative diseases
Nimworaphan, J., Markowitz, D. M., & Sergott, R. C. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1659264 · Cited by 4
“…the “Mitochondrial Cascade Hypothesis” postulates that abnormal mitochondrial function impacts the processing of amyloid precursor protein (APP), a transmembrane protein, and increases A β oligomer production and accumulation, possibly promoting the formation of neurofibrillary tangles (88).”
Mitochondrial-derived microproteins in lung disease: insights and implications
Behan, M., Yen, K., Cohen, P., & Kliment, C. R. (2026) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00369.2025 · Cited by 4
Natural polysaccharides as multifunctional regulators of energy metabolism: mechanisms, structure-activity relationships, and cross-disease applications
Wei, S., Lv, H., Li, X., & Xue, J. (2026) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2026.2660145 · Cited by 4
“Neurons gradually deteriorate due to “energy starvation,” accelerating cognitive decline (Mattson et al. 2008; Swerdlow et al. 2010; Camandola and Mattson 2017).”
MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer’s Disease
Luo, J.-S., Zhai, W.-H., Ding, L.-L., Zhang, X.-J., Han, J., Ning, J., Chen, X.-M., Jiang, W., Yan, R., & Chen, M. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04205-w · Cited by 4
“The secondary mitochondrial cascade hypothesis states that mitochondrial dysfunction is secondary to the amyloid cascade [21, 23].”
Interplay of oxidative stress and mitochondrial dysfunction in Alzheimer’s and Parkinson’s diseases: mechanisms and treatment strategies
Im, M., Klymenko, O. О., Gonchar, O. O., Karasevich, N. V., & In, K. (2023) · Neurophysiology · doi:10.1007/s11062-025-09958-w · Cited by 4
“It has been established that A β peptides accumulate in neuronal mitochondria [32], leading to the inhibition of mitochondrial respiratory complexes II and IV, reduced ATP production, and increased ROS generation [33].”
Role and Function of Dehydrogenases in CNS and Blood-Brain Barrier Pathophysiology
Naik, P. U., Prasad, S., & Cucullo, L. (2012) · InTech eBooks · doi:10.5772/48338 · Cited by 4
“What is of primary interest to us is that it is slowly becoming well accepted that metabolic dysfunction, related oxidative stress and mitochondrial deficits can precede AD development (84-86).”
Background
Aberrant mitochondrial RNA in the role of aging and aging associated diseases
Chen, Y., Parker, W. D., Chen, H., & Yang, K. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.04.022 · Cited by 4
“All these studies suggest mitochondrial changes may work as a driving force, rather than a consequence, of the aging process and AD pathogenesis [38,39].”
Background
Self‐evolving oxidative stress with identifiable pre‐ and postmitochondrial phases in PC12 cells
Zhang, G., Morin, C., Zhu, X., Huynh, M. B., Ouidja, M. O., Sepulveda-Diaz, J. E., Raisman‐Vozari, R., Li, P., & Papy-García, D. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23146 · Cited by 4
“Although the mechanism by which the imbalance is maintained in the ‘‘damaged part’’ might be multifactorial, it has been proposed that, once mitochondria become significantly affected the oxidative process is difficult to reverse (Swerdlow et al., 2010; Martin, 2011).”
Background
Alzheimer’s Disease Therapy: Present and Future Molecules
Kumar, A., & Kumar, A. (2017) · Neuromethods · doi:10.1007/978-1-4939-7404-7_1 · Cited by 4
A Review of the Relationship Between Gut Microbiota and Memory
Benmelouka, A. Y., Sherif, A., & Ebada, M. A. (2019) · Springer eBooks · doi:10.1007/978-981-13-9636-6_8 · Cited by 4
Extending Swerdlow’s hypothesis: statistical models of mitochondrial deterioration and aging
Wallace, R. (2014) · Journal of Mathematical Chemistry · doi:10.1007/s10910-014-0418-x · Cited by 4
“Here we will examine the implications of mitochondrial deterioration for control of protein folding, finding, as described above, mechanisms consistent with Swerdlow’s mitochondrial cascade hypothesis [1].”
BackgroundResultInfluential
Selected reaction monitoring mass spectrometry for relative quantification of proteins involved in cellular life and death processes
Birkler, R. I. D., Nochi, Z., Gregersen, N., & Palmfeldt, J. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.09.017 · Cited by 4
Mitochondrial dysfunction and Ca2+ dysregulation in human iPSC-derived neurons carrying presenilin-1 mutation arise under stress via an MCU-1-independent mechanism
Wilson, C., Galeano, P., Remedi, M. M., Novack, G. V., Campanelli, L., Gastaldi, L., Miglietta, E. A., Rossi, A. H., Olivar, N., Brusco, L. I., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-35597-0 · Cited by 4
The multifaceted role of mitochondrial dysfunction in Alzheimer’s disease pathogenesis
Ebrahimi, R., Mohammadi, I., Ghafourian, K., Firouzabadi, S. R., Saleh, M., Davoody, S., Azad, G., & Esmaeilpour, K. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01850-8 · Cited by 4
The Interplay Between Immunometabolism and Neuroinflammation in Alzheimer’s Disease
Crescenzo, T. D., Papiri, G., Membrino, V., Alia, S., Cecati, M., Campagna, R., Silvestrini, M., Luzzi, S., & Vignini, A. (2026) · Biomolecules · doi:10.3390/biom16050656 · Cited by 3
“Neurons rely predominantly on oxidative phosphorylation to sustain their high energetic demands; therefore, mitochondrial impairment rapidly results in bioener-getic failure, synaptic dysfunction, and ultimately cell death [38].”
Dysregulation of autophagosome–mitochondria contacts contributes to autophagy dysfunction and neurodegeneration in tauopathy
Jia, N., Guan, H., Zuo, Y., Jeong, Y. Y., Amireddy, N., Rajapaksha, G., Gonzalez, C. U., Jaber, N., Lee, Y., Nissenbaum, M., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2520331123 · Cited by 3
The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation
Ling, Y., Hu, L., Chen, J., Zhao, M., & Dai, X. (2024) · Clinics · doi:10.1016/j.clinsp.2024.100373 · Cited by 3
“7,8 Research indicates that FRMD6 can mitigate the toxic damage caused by A β by improving mitochondrial function and structure in hippocampal neurons.”
Background
Incorporating Mitochondrial Gene Expression Changes Within a Testable Mathematical Model for Alzheimer’s Disease: Stress Response Modulation Predicts Potential Therapeutic Targets
Shelton, M. G., Kerns, K. A., Castora, F. J., & Coleman, R. A. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220163 · Cited by 3
Insights into the promising prospect of pharmacological approaches targeting mitochondrial dysfunction in major human diseases: At a glance
Rahman, M. M., Sarker, M. T., Ahmed, S., Uddin, M. N., Islam, M. R., Islam, M. R., Das, S., Mukherjee, N., Hemeg, H. A., Rauf, A., et al. (2023) · Process Biochemistry · doi:10.1016/j.procbio.2023.07.007 · Cited by 4
Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease
Zou, Y., Yu, L., Yu, W., Du, Y., Shi, R., Zhang, M., Duan, J., Deng, Y., Tu, Q., Dai, R., et al. (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000351669 · Cited by 3
Warning SINEs: Alu elements, evolution of the human brain, and the spectrum of neurological diseasePreprint
Larsen, P. A., Hunnicutt, K. E., Larsen, R. J., Yoder, A. D., & Saunders, A. M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/230367 · Cited by 2
Mitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2
Similar Normalizing Effect of HSP70 and YB-1 Stress Proteins on the Brain Transcription of a Mouse Model of Alzheimer’s Disease
Bobkova, N. V., Chuvakova, L. N., Kononova, S. V., Kovalev, V. I., Sukhikh, G. T., Zatsepina, O. G., Rezvykh, A. P., & Евгеньев, М. Б. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05135-6 · Cited by 4
The Relationship Between Diet and the Neuropathological Hallmarks of Alzheimer’s Disease in Cognitively Normal Adults: A Systematic Narrative Review
Harb, A. A., Brock-Spano, K. A., Silverman, J. R., Thomas, J. R., & Pothen, A. S. (2025) · Healthcare · doi:10.3390/healthcare13202628 · Cited by 2
“Our genes and environmental factors determine the rate at which this decline in mitochondrial function occurs [27].”
The rise and deceleration of neuronal excitability in aging and Alzheimer’s disease: Mechanisms, implications, and therapeutic targets
Delbono, O., Wang, Z., & Messi, M. L. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102999 · Cited by 3
Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer’s Pathogenesis
Houfkova, A., & Schmidt, M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05786-z · Cited by 2
Hsp60 Friend and Foe of the Nervous System
Marino, A., Bavisotto, C. C., Rappa, F., Scalia, F., de Macario, E. C., Macario, A. J. L., & Cappello, F. (2019) · Heat shock proteins · doi:10.1007/978-3-030-24285-5_1 · Cited by 2
Nanomedical drug delivery for neurodegenerative disease
Kaur, N., Kumar, V., Mahender, T., Maji, I., Mahajan, S., Aalhate, M., Singh, P. K., & Sahu, S. K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85544-0.00016-2 · Cited by 2
Role of mitochondria in brain functions and related disorders
Yadav, M., Dahiya, M., Dagar, J., Singh, N., Sharma, N., Rawat, N., Dhakla, P., Minocha, N., & Kumar, A. (2022) · Exploration of Medicine · doi:10.37349/emed.2022.00110 · Cited by 2
“A peptide buildup in mitochondria inhibits complex II and IV of the mitochondrial enzyme system, increasing ROS and reducing ATP synthesis [76].”
Background
Cu‐Catalyzed Cross‐Coupling Reactions of Enamines and Terminal Alkynes: Access of Propargylamines as Neurodegenerative Disorder Agents
Mohan, L., Lee, J. E., Srinivasarao, M., Cutright, A. J., Raju, S., Stokes, S. L., Emerson, J. P., & Kim, J. (2023) · Asian Journal of Organic Chemistry · doi:10.1002/ajoc.202300375 · Cited by 2
Nicotine: A Possible Neuroprotector in Brain Disorders
Alkadhi, K. A., Salim, S., & Alzoubi, K. H. (2025) · Springer eBooks · doi:10.1007/978-3-642-36202-6_178-1 · Cited by 2
Alzheimer’s Disease Pathogenic Mechanisms: Linking Redox Homeostasis and Mitochondria-Associated Metabolic Pathways Through Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)
Rostagno, A. A., & Ghiso, J. A. (2025) · Antioxidants · doi:10.3390/antiox14070812 · Cited by 3
“Alterations in mitochondrial dynamics, deficiencies in mitochondrial proteins, changes in mitochondrial membrane potential, and an increase in oxidative stress have been observed associated with the disease [47–49,52,70,85–87]).”
Integrating mitochondrial gene expression data to model the effects of respirasome supercomplex formation on reactive oxygen species production in Alzheimer's disease models
Shelton, M. G., Kerns, K. A., Shirali, S., Castora, F. J., & Coleman, R. A. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251362889 · Cited by 2
Cumulative burden of lifestyle risk factors on Alzheimer's disease in older Korean adults: A nationwide retrospective cohort study
Lee, J., Kim, Y., Kim, W., Cho, S., Kim, J. H., Kim, Y. S., & Kang, S. Y. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251386889 · Cited by 2
“37,38 Similarly, physical inactivity increases oxidative stress and decrease mitochondrial ef ﬁ ciency, and antioxidant capacity, effecting neuronal vulnerability.”
Targeting Mitochondria and Redox Dyshomeostasis in Brain Ageing: An Update
Cardoso, S., & Moreira, P. I. (2021) · Healthy ageing and longevity · doi:10.1007/978-3-030-84965-8_8 · Cited by 2
Proteomics analysis of mitochondrial dysfunction triggered by complex specific electron transport chain inhibitors reveals common pathways involving protein misfolding in an SH-SY5Y in vitro cell model
Şahin, B., & Baykal, A. T. (2017) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-1702-44 · Cited by 2
“It has been suggested that in sporadic AD, mitochondrial dysfunction is the primary event that leads to amyloid-β protein deposition, formation of neurofibrillary tangles, and synaptic degeneration (Swerdlow et al., 2010).”
Background
Telomeres and Oxidative Stress
Nasir, N. F. M., Kannan, T. P., Sulaiman, S. A., Shamsuddin, S., Ahmad, A., & Stângaciu, Ş. (2014) · Journal of Advances in Medicine and Medical Research · doi:10.9734/bjmmr/2014/5548 · Cited by 2
“One of the contributing factors that are common to many neurodegenerative diseases involving oxidative stress pathways is mitochondrial dysfunction which has been reported to cause an increase of ROS production [56-57].”
Background
Psychopharmakotherapie – pharmakologische Grundlagen
Müller, W. E., & Eckert, A. (2016) · Springer eBooks · doi:10.1007/978-3-642-45028-0_30-1 · Cited by 2
Brain Hydrophobic Peptides Antagonists of Neurotoxic Amyloid β Peptide Monomers/Oligomers–Protein Interactions
Gutiérrez‐Merino, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813846 · Cited by 4
“Finally, the mitochondria is an alternate source of peptides in AD since mitochondria dysfunction has been linked to metabolic and oxidative damage in this disease [154,155].”
Stress oxydant et maladie d’Alzheimer
Gilbert, T., Drai, J., & Bonnefoy, M. (2013) · Springer eBooks · doi:10.1007/978-2-8178-0443-9_10 · Cited by 2
Psychopharmakotherapie – pharmakologische Grundlagen
Müller, W. E., & Eckert, A. (2017) · Springer eBooks · doi:10.1007/978-3-662-49295-6_30 · Cited by 2
Mitochondria in Alzheimer disease : regulatory mechanisms and cell death
Hedskog, L. (2012) · Figshare · Cited by 2
Perturbed Brain Energy Metabolism in Alzheimer’s Disease and Diabetes
Wu, L. (2017) · KU ScholarWorks (University of Kansas) · Cited by 2
The Effect of Selected Coffee Constituents on Mitochon-Drial Dysfunction In An Early Alzheimer Disease Cell ModelPreprint
Babylon, L., Limbeck, M. T., & Eckert, G. P. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.20.537643 · Cited by 1
Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neuronsPreprint
Jia, N., Ganesan, D., Guan, H., Jeong, Y. Y., Han, S., Nissenbaum, M., Kusnecov, A. W., & Cai, Q. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.12.579959 · Cited by 2
Selective Disposal of Insoluble Protein Aggregates
Seneci, P. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800186-8.00005-5 · Cited by 1
Exposure to ambient carbon monoxide and cognitive decrease in a memory clinic
Jung, J., Ko, H., Kim, H., Lee, H., & Lee, J. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251372970 · Cited by 1
“31,32 CO exposure can also cause mitochondrial damage, 33,34 which can increase the risk of brain dysfunctions such as AD.”
Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer’s disease
Kara, B., Beck, J. S., Fu, Z., Hickey, S. L., Kanaan, N. M., Mufson, E. J., Ginsberg, S. D., & Counts, S. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02080-2 · Cited by 1
“This concept is in line with the proposed mitochondrial cascade hypothesis for AD pathogenesis and supports the rationale for bioenergetic-centric strategies targeting mitochondrial function as part of a polypharmacological, synaptoprotective, and disease-modifying therapeutic regimen [131].”
The Role of Mitochondria in Consciousness and Cognition: New Insights from Feelings of Knowing-fundamental Interoceptive Patterns Theory
Pollard-Wright, H., & Wright, M. T. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1012466 · Cited by 1
Age at type 2 diabetes onset and risk of dementia: The modifying role of genetic susceptibility and mitochondrial function
Dong, W., Yuan, Q., Wu, B., Gao, S., Zhang, Y., Pan, Y., Zhou, K. S., & Jiang, H. (2026) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2026.100780 · Cited by 1
“The “ mitochondrial cascade hypothesis ” posits that impaired mitochondrial metabolism may be an upstream driver of AD pathology [47,48].”
Targeting tau-mitochondrial crosstalk in Alzheimer’s disease with an Integrative multi-omics and artificial intelligence driven tools for the development of disease-modifying therapeutics
Bhasha, S., Chintada, V., Munikumar, D. M., Maddineni, J., Nagulavancha, R., Malempati, T., Gadda, S. S., Sankepally, K. K. R., & Pradeepkiran, J. A. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103186 · Cited by 1
Endogenous Agents That Contribute to Generate or Prevent Ischemic Damage
Piazza, O., & Scarpati, G. (2012) · InTech eBooks · doi:10.5772/32745 · Cited by 1
Mitochondrial and Golgi Apparatus’ Alterations in Alzheimer’s Disease: A Study of the Cerebellar Cortex Based on Silver Impregnation Technique and Electron Microscopy
Baloyannis, S. J. (2014) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9781608058709114020003 · Cited by 1
Nontargeted Metabolite Profiling of Induced Pluripotent Stem Cells (iPSCs) Derived Neural Cells: Insights Into Mechanisms of Brain Diseases
Lehtonen, Š., Lehtonen, M., & Koıstınaho, J. (2016) · InTech eBooks · doi:10.5772/62851
Melatonin Supplementation in Neurodegenerative Diseases: Current Status
Polimeni, G., Guarneri, C., & Cuzzocrea, S. (2016) · Springer eBooks · doi:10.1007/978-81-322-2803-5_6 · Cited by 1
Mitochondrial abnormalities in neurological disorders
Ferreira, A. F. F., Singulani, M. P., & de Britto, L. R. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822416-8.00012-9 · Cited by 1
Mitophagy Impairments as Culprit of Alzheimer’s Disease
Mani, S., Swargiary, G., Singh, M., & Rawal, M. (2022) · Springer eBooks · doi:10.1007/978-981-16-7606-2_5 · Cited by 1
An analysis of neurovascular disease markers in the hippocampus of Tupaia chinensis at different growth stages
Ouyang, Y., Zhang, Y., Guo, X., Li, J., Ao, Q., Guo, S., Zhang, M., & Sun, J. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2022.1083182 · Cited by 1
The interaction between microglial dysfunction and mitochondrial impairment in Alzheimer’s disease
Luo, Q., Noh, J. H., & Sima, J. (2023) · Aging Research · doi:10.26599/agr.2023.9340020 · Cited by 1
Pathophysiology and Management Approaches in Alzheimer’s Disease
Jain, S., Goel, D., Nazir, S. S., Yadav, V., & Vohora, D. (2023) · Springer eBooks · doi:10.1007/978-981-99-6807-7_4 · Cited by 2
Neuron Foundry Mach 8: A Concept of Multi-modal Neuro-supportive Energy Therapy Device for Treating Neurodegenerative Disorders
McGlynn, C., Dermawan, D., & Canonizado, G. M. (2024) · Brain Science Advances · doi:10.26599/bsa.2023.9050026 · Cited by 1
“Recent research has underscored the importance of energy dysregulation in these diseases [99].”
STARRING ROLE OF MITOCHONDRIAL IMPAIRMENT IN ALZHEIMER’S DISEASE NEUROPATHOLOGY
Yousaf, A., Deeba, F., Younis, S., Iqbal, N., & Aslam, F. (2022) · THE JOURNAL OF MICROBIOLOGY AND MOLECULAR GENETICS · doi:10.52700/jmmg.v3i2.70 · Cited by 1
Therapeutic promise of α-hederin in Alzheimer’s disease: Insights into inflammation, oxidative stress, and apoptosis modulation
Chettupalli, A. K., Gupta, N., Bukke, S. P. N., Singh, M. P., & Mandal, C. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118803 · Cited by 1
The Role of Nitric Oxide on Vascular Dysfunction During Aging and Alzheimer’s Disease
Venturelli, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816545-4.00011-6 · Cited by 1
Role of Immunotherapy in Ameliorating Proteopathic Dementia
Singh, M., Pancham, P., Agarwal, S., Kaur, H., Agarwal, V., Tiwari, R. K., Mani, S., & Rachana, R. (2022) · Springer eBooks · doi:10.1007/978-981-16-7606-2_16 · Cited by 1
Medicinal Cannabis for Alzheimer's Disease
Steiner, G. Z., Coles, M., Jaye, K. M., Metri, N., Butt, A. S., Christofides, K., McPartland, J., Al-Modhefer, Z., Karamacoska, D., Russo, E. B., et al. (2023) · Advances in medical diagnosis, treatment, and care (AMDTC) book series · doi:10.4018/978-1-6684-5652-1.ch001 · Cited by 1
Deficits in mitochondrial function and glucose metabolism seen in sporadic and familial Alzheimer’s disease derived Astrocytes are ameliorated by increasing hexokinase 1 expression
Bell, S. M., Wareing, H., Hamshaw, A., De, S., New, E., Shaw, P. J., De Marco, M., Venneri, A., Blackburn, D. J., Ferraiuolo, L., et al. (2023) · doi:10.1101/2023.03.23.534020 · Cited by 1
Balanced deep learning on multi-omics networks identifies molecular subgroups of pathological brain agingPreprint
Nsangou, Y. A. N., Wörheide, M. A., Seyfried, N. T., Dönitz, J., Kaddurah‐Daouk, R., Kastenmüller, G., & Arnold, M. (2026) · medRxiv · doi:10.64898/2026.02.18.26346567 · Cited by 1
Sinalização intracelular desencadeada por concentrações subtóxicas de estreptozotocina em células neuro-2A: modelo in vitro de neurodegeneração associada à doença de Alzheimer.
Mazucanti, C. H. (2013) · doi:10.11606/d.42.2013.tde-26092013-102423
A life span approach to the relationship between cholesterol, late onset Alzheimer's disease, and cognitive functioning among older adults
Downer, B. G. (2014) · UKnowledge (University of Kentucky)
Melatonin in Alzheimer’s Disease: Focus on Neuroprotective Role
Srinivasan, V., Lauterbach, E. C., Kaur, C., Ahmad, A. H., Mohamed, M., Prasad, A., & Shillcutt, S. D. (2013) · Springer eBooks · doi:10.1007/978-81-322-0825-9_16
Fisiopatología mitocondrial en la sepsis experimental: papel de la óxido nítrico sintasa mitocondrial constitutiva y la melatonina
García, O., & José, F. (2013) · Institutional Repository of the University of Granada (University of Granada)
Molecular Mechanisms of Tau Protein Aggregation Inhibition
Akoury, E. (2013) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-4145
Neuroprotective Effect of Genistein : Studies in Rat Models of Parkinson’s and Alzheimer’s Disease
Bagheri, M. (2012) · DiVA (Linkoping University)
Pathological Consequences of Aβ From Extracellular to Intraneuronal
D’Andrea, M. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804256-4.00004-8
Alzheimer’s disease: Risk factors and therapeutic targets
Pokhrel, L. (2015) · Journal of Coastal Life Medicine · doi:10.12980/jclm.3.2015j5-57
“Some reports have mentioned that the age dependent reduced effectiveness of mitochondria leads to the late onset of AD[45].”
Background
Toxicant-Induced Mitochondrial Dysfunction and Dopaminergic Neurodegeneration in Caenorhabditis elegans
González-Hunt, C. P. (2017) · DukeSpace (Duke University)
Efeito do agonista seletivo do receptor canabinoide 1 (CB1) em modelos de neurodegeneração induzida pela estreptozotocina.
Crunfli, F. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2018.tde-14032018-110624
Mitochondria and Neurodegenerative Diseases
Johri, A., & Chandra, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11474-6
a Circulating cell free mitochondrial DNA copy number variation in neurodegenerative disease
Lowes, H. (2018)
Pathways of neurodegeneration underlying dementia
Buckley, N. J., & Tofaris, G. K. (2020) · doi:10.1093/med/9780198713005.003.0038

Authors: Swerdlow, R. H., Burns, J. M., & Khan, S. M.
Affiliations: University of Kansas (US)
Gencia (United States) (US)
Corresponding author: Swerdlow, Russell H.
ORCID: Swerdlow, Russell H.
Burns, Jeffrey M.
Venue: Journal of Alzheimer s Disease
Publisher: SAGE Publications
Published: 2010-06-03
Volume: 20
Issue: s2
Pages: S265-S279
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2010-100339
PMC: PMC2883665
OpenAlex: W1685999671
Cited by: 562
References: 145
Citations by year: 2026: 31 · 2025: 30 · 2024: 26 · 2023: 63 · 2022: 34 · 2021: 37 · 2020: 38 · 2019: 25 · 2018: 36 · 2017: 37 · 2016: 41 · 2015: 31 · 2014: 33 · 2013: 37 · 2012: 28
FWCI: 3.21
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0/ (unspecified)
Locations: Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (AG026374, R21AG029615, AG029615, AG022407, R01AG022407, R03AG026374)
National Eye Institute (R21EY018474, EY018474)
National Institute of Neurological Disorders and Stroke (K23NS058252)
National Center for Research Resources (M01RR023940)
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
MeSH terms: Aging, Alzheimer Disease, Animals, Electron Transport Complex IV, DNA, Mitochondrial, Humans, Mitochondria, Models, Biological, Amyloid beta-Peptides

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

The Alzheimer’s Disease Mitochondrial Cascade Hypothesis

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks