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The Alzheimer’s Disease Mitochondrial Cascade Hypothesis
Open accessAbstract
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.
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In the citing paper
“Models based on early-onset, autosomal dominant AD may therefore provide limited insight into late-onset, non-autosomal dominant AD.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“In other words, toxic cascades in AD are not initiated by Aβ, but by mitochondria.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“If correct, the mitochondrial cascade hypothesis has several inconvenient implications. The main implication is that early-onset, autosomal dominant and late-onset, non-autosomal dominant AD cases do not share a common etiology.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“According to the hypothesis Aβ is not an “upstream” biomarker of AD, but is instead a “downstream” marker of evolving mitochondrial dysfunction.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“Accordingly, Aβ deposition within an aging brain simply indicates critical age-related changes are occurring.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“According to the mitochondrial cascade hypothesis, mitochondrial function constitutes the crucial link between brain aging and AD.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“It deviates from the amyloid cascade hypothesis by predicting age-related changes in mitochondrial function, rather than mutations or polymorphisms in APP or Aβ processing genes, primarily account for age-associated brain Aβ changes.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“When mitochondrial decline surpasses a threshold compensatory mechanisms fail and late-onset AD ensues.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“The mitochondrial cascade hypothesis proposes mitochondrial function declines with age, and this decline promotes some features of brain aging including Aβ accumulation.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“In contrast to the amyloid cascade hypothesis, which views Aβ as the primary upstream AD biomarker, the mitochondrial cascade hypothesis in general sees Aβ more as a downstream biomarker of brain aging.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“The mitochondrial cascade hypothesis proposes mitochondrial function declines with age, and this decline promotes some features of brain aging including Aβ accumulation.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [146]
In the citing paper
“In this explanation, the mitochondrial function declines with age and leads to increased production of ROS [65,66].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [66]
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Citations
Cites
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
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].”
BackgroundGoate, 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].”
BackgroundQuerfurth, 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].”
BackgroundPremature 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].”
BackgroundResultScheuner, 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].”
BackgroundCandidate 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
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165 · cited 2×
“to speculate somatic mtDNA mutation contributes to age-related declines in mitochondrial function, and available data support this view [38,50].”
BackgroundResultOxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055 · cited 1×
“Mitochondria are the single greatest source of cell free radical production [68].”
BackgroundWolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., & Selkoe, D. J. (1999) · Nature · doi:10.1038/19077 · Cited by 1,959
Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · cited 1×
“oligomers consisting of the 42 amino acid Aβ derivative (Aβ42) are believed to be critical [3].”
BackgroundHuman Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
King, M. P., & Attardi, G. M. (1989) · Science · doi:10.1126/science.2814477 · Cited by 1,685 · cited 1×
“During the 1990s we used a cytoplasmic hybrid (cybrid) approach [23] to address whether mitochondrial DNA (mtDNA) could at least partly account for the systemic AD cytochrome oxidase defect (Fig.”
MethodEvans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627
Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1769 · Cited by 1,570 · cited 1×
“Increased mtDNA deletion abundance has also been demonstrated in Parkinson’s disease substantia nigra and is believed by some to contribute to that neurodegenerative disease [55,56].”
BackgroundAmyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565 · cited 1×
“Interstitial fluid Aβ levels also vary with sleepwake cycles; in mice, wakefulness associates with increased interstitial fluid Aβ, and sleep associates with decreased interstitial fluid Aβ [85].”
BackgroundHolmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61075-2 · Cited by 1,416 · cited 1×
“Results from several recent anti-amyloid clinical trials are consistent with this view [134,135,136, 137,138].”
BackgroundHuman cells lacking mtDNA: repopulation with exogenous mitochondria by complementation
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90040-d · Cited by 1,386
Mitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367 · cited 2×
“The COX10 knock out mice showed profound reductions in COX1 protein and oxidative stress, whereas AD brains show profound increases in COX1 protein and oxidative stress [57].”
BackgroundClinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000159740.16984.3c · Cited by 1,329
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303
Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease
Wang, X., Su, B., Lee, H.-G., Li, X., Perry, G., Smith, M. A., & Zhu, X. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1357-09.2009 · Cited by 1,224
Manczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104
Positron Emission Tomography in Evaluation of Dementia
Silverman, D. H. S., Small, G. W., Chang, C. Y., Lu, C. S., de Aburto, M. A. K., Chen, W., Czernin, J. G., Rapoport, S. I., Pietrini, P., Alexander, G. E., et al. (2001) · JAMA · doi:10.1001/jama.286.17.2120 · Cited by 960 · cited 1×
“One ligand, a fluoro-labeled glucose analog called fluoro-2-deoxy-D-glucose (FDG), shows differences between AD and control subject brain glucose utilization [42].”
BackgroundDu, H., Guo, L., Fang, F., Chen, D., Sosunov, A. A., McKhann, G. M., Yan, Y., Wang, C., Zhang, H., Molkentin, J. D., et al. (2008) · Nature Medicine · doi:10.1038/nm.1868 · Cited by 950
The incidence of dementia: A meta-analysis
Jorm, A. F., & Jolley, D. (1998) · Neurology · doi:10.1212/wnl.51.3.728 · Cited by 903
Age, Neuropathology, and Dementia
Savva, G. M., Wharton, S. B., Ince, P. G., Forster, G., Matthews, F. E., & Brayne, C. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0806142 · Cited by 900 · cited 1×
“Many non-demented elderly individuals also have plaques and tangles [28,34].”
BackgroundKraytsberg, Y., Kudryavtseva, E., McKee, A. C., Geula, C., Kowall, N. W., & Khrapko, K. (2006) · Nature Genetics · doi:10.1038/ng1778 · Cited by 896 · cited 1×
“Increased mtDNA deletion abundance has also been demonstrated in Parkinson’s disease substantia nigra and is believed by some to contribute to that neurodegenerative disease [55,56].”
BackgroundKatzman, R. (1986) · New England Journal of Medicine · doi:10.1056/nejm198604103141506 · Cited by 801
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 · cited 1×
“An increasing number of studies report APP and Aβ associate with mitochondria [75,76,77, 78,79,80,81,82].”
BackgroundLinkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.
(1991) · Europe PMC (PubMed Central) · Cited by 758
A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · cited 4×
“tempts to explain how and why sporadic AD develops [15,16].”
BackgroundInfluentialA phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753
Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease
Caspersen, C., Wang, N., Yao, J., Sosunov, A., Chen, X., Lustbader, J. W., Xu, H. W., Stern, D., McKhann, G., & Du Yan, S. (2005) · The FASEB Journal · doi:10.1096/fj.05-3735fje · Cited by 738 · cited 1×
“An increasing number of studies report APP and Aβ associate with mitochondria [75,76,77, 78,79,80,81,82].”
BackgroundHansson Petersen, C. A., Alikhani, N., Behbahani, H., Wiehager, B., Pavlov, P. F., Alafuzoff, I., Leinonen, V., Ito, A., Winblad, B., Glaser, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806192105 · Cited by 693
The mitochondrial energy transduction system and the aging process
Navarro, A., & Boveris, A. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00213.2006 · Cited by 646 · cited 4×
“It is generally accepted that mitochondrial function declines with age [37].”
BackgroundInfluentialGreen, R. C. (2009) · JAMA · doi:10.1001/jama.2009.1866 · Cited by 643 · cited 1×
“Results from several recent anti-amyloid clinical trials are consistent with this view [134,135,136, 137,138].”
BackgroundThe Prevalence and Malignancy of Alzheimer Disease
Katzman, R. (1976) · Archives of Neurology · doi:10.1001/archneur.1976.00500040001001 · Cited by 623
Evans, D. A., Funkenstein, H. H., Albert, M., Scherr, P. A., Cook, N. R., Chown, M. J., Hebert, L. E., Hennekens, C. H., & Taylor, J. O. (1989) · PubMed · Cited by 599
Cytochrome oxidase deficiency in Alzheimer’s disease
Parker, W. D., Filley, C. M., & Parks, J. K. (1990) · Neurology · doi:10.1212/wnl.40.8.1302 · Cited by 598 · cited 2×
“Reduced AD subject cytochrome oxidase activity was first reported in 1990 [20].”
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 · cited 1×
“An increasing number of studies report APP and Aβ associate with mitochondria [75,76,77, 78,79,80,81,82].”
BackgroundCraft, S., Peskind, E., Schwartz, M. W., Schellenberg, G. D., Raskind, M., & Porte, D. (1998) · Neurology · doi:10.1212/wnl.50.1.164 · Cited by 560
Coskun, P. E., Beal, M. F., & Wallace, D. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403649101 · Cited by 556 · cited 1×
“Mutation levels of heteroplasmic, presumably somatic mtDNA control region mutations were elevated in AD subject brains [52].”
BackgroundHenderson, S. T., Vogel, J. L., Barr, L. J., Garvin, F., Jones, J. J., & Costantini, L. C. (2009) · Nutrition & Metabolism · doi:10.1186/1743-7075-6-31 · Cited by 548
Brain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · cited 1×
“The AD cytochrome oxidase defect was first demonstrated in AD subject platelet mitochondria, and later shown to occur in the AD brain [21,22].”
BackgroundA PHASE 2 MULTIPLE ASCENDING DOSE TRIAL OF BAPINEUZUMAB IN MILD TO MODERATE ALZHEIMER DISEASE
Laskowitz, D., & Kolls, B. J. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e03844 · Cited by 522 · cited 1×
“Results from several recent anti-amyloid clinical trials are consistent with this view [134,135,136, 137,138].”
BackgroundPrevalence and Malignancy of Alzheimer Disease
Lijtmaer, H., Fuld, P. A., & Katzman, R. (1976) · Archives of Neurology · doi:10.1001/archneur.1976.00500040088017 · Cited by 517
Stewart, R., Masaki, K., Xue, Q.-L., Peila, R., Petrovitch, H., White, L. R., & Launer, L. J. (2005) · Archives of Neurology · doi:10.1001/archneur.62.1.55 · Cited by 478
Morris, J. C., Roe, C. M., Grant, E. A., Head, D., Storandt, M., Goate, A. M., Fagan, A. M., Holtzman, D. M., & Mintun, M. A. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.269 · Cited by 476 · cited 1×
“Some propose such individuals have very early AD in which detectable dementia has not yet manifested [35,36].”
BackgroundAlzheimer's disease: the two-hit hypothesis
Zhu, X., Raina, A. K., Perry, G. L., & Smith, M. A. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00707-0 · Cited by 431 · cited 1×
“Some believe oxidative stress, either by itself or as part of a “two hit process”, causes AD [14].”
BackgroundGibson, G. E., Sheu, K. ‐. R., Blass, J. P., Baker, A., Carlson, K., Harding, B. N., & Perrino, P. (1988) · Archives of Neurology · doi:10.1001/archneur.1988.00520320022009 · Cited by 425 · cited 1×
“Deficiencies of two Krebs cycle enzymes, pyruvate dehydrogenase complex and ketoglutarate dehydrogenase complex, were reported in the 1980's [17,18,19].”
BackgroundReduced Lean Mass in Early Alzheimer Disease and Its Association With Brain Atrophy
Burns, J. M., Johnson, D. K., Watts, A. S., Swerdlow, R. H., & Brooks, W. M. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.38 · Cited by 408
Change in body mass index and risk of incident Alzheimer disease
Buchman, A. S., Wilson, R. S., Bienias, J. L., Shah, R. C., Evans, D. A., & Bennett, D. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176061.33817.90 · Cited by 407 · cited 1×
“Systemic manifestations Weight loss manifests early in AD and during the lead-up to it [105,106,107,108,109,110,111, 112,113,114].”
BackgroundDecreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain
Sorbi, S., Bird, E. D., & Blass, J. P. (1983) · Annals of Neurology · doi:10.1002/ana.410130116 · Cited by 400 · cited 1×
“Deficiencies of two Krebs cycle enzymes, pyruvate dehydrogenase complex and ketoglutarate dehydrogenase complex, were reported in the 1980's [17,18,19].”
BackgroundA TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease
Roses, A. D., Lutz, M. W., Amrine‐Madsen, H., Saunders, A. M., Crenshaw, D. G., Sundseth, S. S., Huentelman, M. J., Welsh-Bohmer, K. A., & Reiman, E. M. (2009) · The Pharmacogenomics Journal · doi:10.1038/tpj.2009.69 · Cited by 391 · cited 1×
“It now appears polymorphisms in a neighboring gene, TOMM40, associate with AD risk [99, 100,101].”
BackgroundPathogenesis of Alzheimer’s Disease
Rostagno, A. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010107 · Cited by 391
Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans
BENEDICTIS, G. D., Rose, G., Carrieri, G., Luca, M. D., Falcone, E., Passarino, G., Bonafè, M., Monti, D., Baggio, G., Bertolini, S., et al. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.12.1532 · Cited by 390 · cited 1×
“Genetic association studies report mtDNA polymorphisms and haplogroups influence longevity; mtDNA haplogroups may also influence AD risk [94,95].”
BackgroundOxidative stress increases expression and activity of BACE in NT2 neurons
Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., et al. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0515 · Cited by 385 · cited 1×
“These findings are not surprising; the effects of oxidative stress on kinase and β-secretase activation are well recognized [66,67].”
BackgroundPotkin, S. G., Guffanti, G., Lakatos, A., Turner, J. A., Kruggel, F., Fallon, J. H., Saykin, A. J., Orro, A., Lupoli, S., Salvi, E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006501 · Cited by 376 · cited 1×
“It now appears polymorphisms in a neighboring gene, TOMM40, associate with AD risk [99, 100,101].”
BackgroundGabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36875-8 · Cited by 373 · cited 1×
“Treating cells with sodium azide, a cytochrome oxidase inhibitor, shifts AβPP processing to an amyloidogenic derivative [63,64].”
BackgroundHigh aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain
Lin, M. T. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.2.133 · Cited by 366 · cited 1×
“Young control, elderly control, and late-onset AD autopsy brains were evaluated for homoplasmic and heteroplasmic COX2 gene mutations [51].”
BackgroundCardiorespiratory fitness and brain atrophy in early Alzheimer disease.
Burns, J. M., Cronk, B. B., Anderson, H. S., Donnelly, J. E., Thomas, G. P., Harsha, A., Brooks, W. M., & Swerdlow, R. H. (2008) · Neurology · doi:10.1212/01.wnl.0000317094.86209.cb · Cited by 363
Self-citationAccelerated Weight Loss May Precede Diagnosis in Alzheimer Disease
Johnson, D. K., Wilkins, C. H., & Morris, J. C. (2006) · Archives of Neurology · doi:10.1001/archneur.63.9.1312 · Cited by 350 · cited 1×
“Systemic manifestations Weight loss manifests early in AD and during the lead-up to it [105,106,107,108,109,110,111, 112,113,114].”
BackgroundWang, X., Su, B., Fujioka, H., & Zhu, X. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.071208 · Cited by 341
Copper-Dependent Inhibition of Human Cytochrome c Oxidase by a Dimeric Conformer of Amyloid-β1-42
Crouch, P. J., Blake, R., Duce, J. A., Ciccotosto, G. D., Li, Q.-X., Barnham, K. J., Curtain, C. C., Cherny, R. A., Cappai, R., Dyrks, T., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4276-04.2005 · Cited by 327
Chang, S., Ma, T. R., Miranda, R. D., Balestra, M. E., Mahley, R. W., & Huang, Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508254102 · Cited by 319 · cited 1×
“tein E or its degradation products also appear to influence mitochondrial function [102].”
BackgroundDoes insulin dysfunction play a role in Alzheimer's disease?
Gasparini, L. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02037-0 · Cited by 314 · cited 1×
“Accumulating evidence suggests insulin signaling is altered in AD [126].”
BackgroundClerk, A., Fuller, S. J., Michael, A., & Sugden, P. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7228 · Cited by 314 · cited 1×
“These findings are not surprising; the effects of oxidative stress on kinase and β-secretase activation are well recognized [66,67].”
BackgroundMarked changes in mitochondrial DNA deletion levels in Alzheimer brains
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., McKee, A. C., Beal, M. F., Graham, B. H., & Wallace, D. C. (1994) · Genomics · doi:10.1006/geno.1994.1525 · Cited by 309 · cited 1×
“Relative to age-matched control brains, mtDNA deletion levels are elevated in AD subject brains [53,54].”
BackgroundPET amyloid ligand [ 11 C]PIB uptake is increased in mild cognitive impairment
Kemppainen, N. M., Aalto, S., Wilson, I. A., Någren, K., Helin, S., Brück, A., Oikonen, V., Kailajärvi, M., Scheinin, M., Viitanen, M. H., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000260969.94695.56 · Cited by 307 · cited 1×
“ing the MCI phase of AD [91,92], and even before.”
BackgroundAmyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Brody, D. L., Magnoni, S., Schwetye, K. E., Spinner, M. L., Esparza, T. J., Stocchetti, N., Zipfel, G. J., & Holtzman, D. M. (2008) · Science · doi:10.1126/science.1161591 · Cited by 295 · cited 1×
“On the contrary, neurologic recovery from acute brain injury associates with increased Aβ production [89].”
BackgroundAnalysis of European mitochondrial haplogroups with Alzheimer disease risk
van der Walt, J. M., Dementieva, Y. A., Martin, E. R., Scott, W. K., Nicodemus, K. K., Kroner, C. C., Welsh-Bohmer, K. A., Saunders, A. M., Roses, A. D., Small, G. W., et al. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.04.051 · Cited by 280 · cited 1×
“Genetic association studies report mtDNA polymorphisms and haplogroups influence longevity; mtDNA haplogroups may also influence AD risk [94,95].”
BackgroundCybrids in Alzheimer's disease: a cellular model of the disease?
Swerdlow, R. H., Parks, J. K., Cassarino, D. S., Maguire, D. J., Maguire, R. S., Bennett, J. P., Davis, R. E., & Parker, W. D. (1997) · Neurology · doi:10.1212/wnl.49.4.918 · Cited by 272
Self-citationWeight Loss Precedes Dementia in Community‐Dwelling Older Adults
Barrett-Connor, E. L., Edelstein, S. L., Corey‐Bloom, J., & Wiederholt, W. C. (1996) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1996.tb01362.x · Cited by 266
Mitochondria dysfunction of Alzheimer's disease cybrids enhances Aβ toxicity
Cardoso, S. M., Santana, I. J., Swerdlow, R. H., & Oliveira, C. R. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02438.x · Cited by 262 · cited 1×
“Azide-mediated cytochrome oxidase inhibition increases free radical production [69], and oxygen radical production is increased in AD cybrid cell lines with reduced cytochrome oxidase Vmax activities [24, 70].”
BackgroundCybrids in Alzheimer's disease: A cellular model of the disease?
Swerdlow, R. H., & Parker, D. W. (1998) · Neurology · doi:10.1212/wnl.51.1.326-a · Cited by 260
Kimberly, W. T., Xia, W., Rahmati, T., Wolfe, M. S., & Selkoe, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.5.3173 · Cited by 253 · 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].”
BackgroundSheehan, J. P., Swerdlow, R. H., Miller, S. W., Davis, R. E., Parks, J. K., Parker, W. D., & Tuttle, J. B. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04612.1997 · Cited by 249 · cited 1×
“We isolated platelets from AD and age-matched control subjects and fused those platelets with both human neuroblastoma SH-SY5Y cells and human NT2 teratocarcinoma cells depleted of their endogenous mtDNA [24,25].”
MethodPathogenesis of Alzheimer's disease.
Swerdlow, R. H. (2007) · PubMed Central · Cited by 237
Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism
Mosconi, L., Brys, M., Switalski, R., Mistur, R., Glodzik, L., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705036104 · Cited by 237 · cited 1×
“Mosconi and colleagues used PET to study AD endophenotypes in middle-aged individuals without an AD diagnosis [43].”
BackgroundPerry, E. K., Perry, R. H., Tomlinson, B. E., Blessed, G., & Gibson, P. H. (1980) · Neuroscience Letters · doi:10.1016/0304-3940(80)90220-7 · Cited by 236 · cited 1×
“Deficiencies of two Krebs cycle enzymes, pyruvate dehydrogenase complex and ketoglutarate dehydrogenase complex, were reported in the 1980's [17,18,19].”
BackgroundMitochondrial DNA damage as a mechanism of cell loss in Alzheimer's disease
de la Monte, S. M., Luong, T., Neely, T. R., Robinson, D., & Wands, J. R. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780140 · Cited by 227 · cited 1×
“els of retrievable, intact mtDNA are reduced in AD brains [58,59].”
BackgroundWeight Change in Alzheimer's Disease
White, H. K., Pieper, C. F., Schmader, K. E., & Fillenbaum, G. G. (1996) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1996.tb00912.x · Cited by 227 · cited 1×
“Systemic manifestations Weight loss manifests early in AD and during the lead-up to it [105,106,107,108,109,110,111, 112,113,114].”
BackgroundIncident dementia in women is preceded by weight loss by at least a decade
Knopman, D. S., Edland, S. D., Cha, R. H., Petersen, R. C., & Rocca, W. A. (2007) · Neurology · doi:10.1212/01.wnl.0000267661.65586.33 · Cited by 226
Xia, W., Yang, T., Shankar, G. M., Smith, I. M., Shen, Y., Walsh, D. M., & Selkoe, D. J. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.565 · Cited by 218 · cited 2×
“While a systemic increase in body Aβ levels could cause this, in AD Aβ levels actually drop in some tissues [27].”
BackgroundCardiorespiratory Fitness and Preserved Medial Temporal Lobe Volume in Alzheimer Disease
Honea, R. A., Thomas, G., Harsha, A., Anderson, H. S., Donnelly, J. E., Brooks, W. M., & Burns, J. M. (2009) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31819cb8a2 · Cited by 217 · cited 1×
“This correlates with brain atrophy and is not due to differences in cognitive function or baseline physical activity [124,125].”
BackgroundAnnonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons
Escobar-Khondiker, M., Höllerhage, M., Muriel, M., Champy, P., Bach, A., Depienne, C., Respondek, G., Yamada, E. S., Lannuzel, A., Yagi, T., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1644-07.2007 · Cited by 212 · cited 1×
“Tau phosphorylation increases in rats and cultured neurons exposed to ETC inhibitors [60,61,62].”
BackgroundThe Alzheimer's disease mitochondrial cascade hypothesis: an update
Swerdlow, R. H., & Khan, S. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.01.011 · Cited by 206 · cited 6×
“In developing our hypothesis, we have therefore considered aging theory and how it may relate to late-onset AD [15,16].”
BackgroundInfluentialThe mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy
Höglinger, G. U., Lannuzel, A., Escobar-Khondiker, M., Michel, P. P., Duyckaerts, C. J., Féger, J., Champy, P., Prigent, A., Medja, F., Lombès, A., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03493.x · Cited by 206 · cited 1×
“Tau phosphorylation increases in rats and cultured neurons exposed to ETC inhibitors [60,61,62].”
BackgroundFunctional mitochondria are required for amyloid β‐mediated neurotoxicity
Cardoso, S. M., Santos, S., Swerdlow, R. H., & Oliveira, C. R. (2001) · The FASEB Journal · doi:10.1096/fj.00-0561fje · Cited by 203 · cited 1×
“In one study particularly relevant to this discussion, NT2 wild type and NT2 ρ0 cells were exposed to Aβ42 protein oligomers [79].”
Backgroundβ‐Amyloid fragment 25–35 selectively decreases complex IV activity in isolated mitochondria
Canevari, L., Clark, J. B., & Bates, T. E. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01028-5 · Cited by 196
Regulation of neuron mitochondrial biogenesis and relevance to brain health
Onyango, I. G., Lu, J., Rodova, M., Lezi, E., Crafter, A. B., & Swerdlow, R. H. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.014 · Cited by 190 · cited 1×
“Efforts to date have been hindered by an incomplete understanding of the mechanisms that mediate brain mitochondrial biogenesis, as well as a dearth of compounds that induce brain mitochondrial biogenesis at brain-achievable concentrations [133,135].”
BackgroundMosconi, L., Mistur, R., Switalski, R., Brys, M., Glodzik, L., Rich, K., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2009) · Neurology · doi:10.1212/01.wnl.0000333247.51383.43 · Cited by 188 · cited 1×
“greater longitudinal CMRglu reductions than FH- or FHp subjects [44].”
BackgroundFukui, H., Diaz, F., Garcia, S., & Moraes, C. T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705738104 · Cited by 185 · cited 1×
“nundrum using genetically altered mice [88].”
Rosiglitazone Induces Mitochondrial Biogenesis in Mouse Brain
Strum, J. C., Shehee, R., Virley, D. J., Richardson, J. C., Mattie, M. D., Selley, P., Ghosh, S., Nock, C. M., Saunders, A. M., & Roses, A. D. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11108 · Cited by 183
Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways.
Khan, S. M., Cassarino, D. S., Abramova, N. N., Keeney, P. M., Borland, M. K., Pa, T., Krebs, C. T., Bennett, J. C., Parks, J. K., Swerdlow, R. H., et al. (2000) · PubMed · Cited by 176
Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment
Valla, J., Schneider, L., Niedzielko, T., Coon, K. D., Caselli, R., Sabbagh, M. N., Ahern, G. L., Baxter, L., Alexander, G., Walker, D. G., et al. (2006) · Mitochondrion · doi:10.1016/j.mito.2006.10.004 · Cited by 159 · cited 1×
“ing the MCI phase of AD [91,92], and even before.”
BackgroundYu, C., Seltman, H. J., Peskind, E. R., Galloway, N. M., Zhou, P. X., Rosenthal, E. A., Wijsman, E. M., Tsuang, D. W., Devlin, B., & Schellenberg, G. D. (2007) · Genomics · doi:10.1016/j.ygeno.2007.02.002 · Cited by 158 · cited 1×
“It now appears polymorphisms in a neighboring gene, TOMM40, associate with AD risk [99, 100,101].”
BackgroundIs aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?
Swerdlow, R. H. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.021 · Cited by 154 · cited 3×
“Late onset AD typically demonstrates neither clearcut Mendelian nor maternal inheritance [28].”
BackgroundValla, J., Yaari, R., Wolf, A. B., Kusne, Y., Beach, T. G., Roher, A. E., Corneveaux, J. J., Huentelman, M. J., Caselli, R. J., & Reiman, E. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100129 · Cited by 150
Edland, S. D., Silverman, J. M., Peskind, E. R., Tsuang, D., Wijsman, E., & Morris, J. C. (1996) · Neurology · doi:10.1212/wnl.47.1.254 · Cited by 145 · cited 2×
“This phenomenon persists after correcting for increased female longevity and higher rates of AD among women [40].”
BackgroundResultGenetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese
Takei, N., Miyashita, A., Tsukie, T., Arai, H., Asada, T., Imagawa, M., Shoji, M., Higuchi, S., Urakami, K., Kimura, H., et al. (2009) · Genomics · doi:10.1016/j.ygeno.2009.01.003 · Cited by 143
Mosconi, L., Rinne, J. O., Tsui, W. H., Berti, V., Li, Y., Wang, H., Murray, J., Scheinin, N., Någren, K., Williams, S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914141107 · Cited by 135 · cited 2×
“PIB PET imaging reveals amyloid accumulates in the middle aged children of asymptomatic at least some AD subjects [47].”
BackgroundMitochondria in cybrids containing mtDNA from persons with mitochondriopathies
Swerdlow, R. H. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21167 · Cited by 128 · cited 2×
“Cybrid studies suggest at least part of the AD cytochrome oxidase defect is a consequence of mtDNA encoding [24,26].”
BackgroundMitochondria in Alzheimer's disease
Swerdlow, R. H., & Kish, S. J. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)53013-0 · Cited by 126 · cited 2×
“The AD cytochrome oxidase defect was first demonstrated in AD subject platelet mitochondria, and later shown to occur in the AD brain [21,22].”
BackgroundGoldberg, R. J. (1996) · Archives of Internal Medicine · doi:10.1001/archinte.156.5.505 · Cited by 125
A comparison of familial and sporadic Alzheimer's disease
Duara, R., Lopez-Alberola, R. F., Barker, W. W., Loewenstein, D. A., Zatinsky, M., Eisdorfer, C. E., & Weinberg, G. B. (1993) · Neurology · doi:10.1212/wnl.43.7.1377 · Cited by 122 · cited 1×
“This was not entirely consistent with available epidemiologic data indicating both parents contribute to their children’s lifetime AD risk [39], but by the mid 1990s several studies reported among late onset AD subjects who report an AD-affected or demented parent, the affected parent is more often a mother [40, 41].”
ResultPeripheral insulin and brain structure in early Alzheimer disease
Burns, J. M., Donnelly, J. E., Anderson, H. S., Mayo, M. S., Spencer-Gardner, L. S., Thomas, G., Cronk, B. B., Haddad, Z., Klima, D., Hansen, D., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000276952.91704.af · Cited by 120 · cited 1×
“We examined relationships between peripheral insulin, cognitive function, and brain volume in non-diabetic AD subjects [128].”
BackgroundThe Thiazolidinedione Pioglitazone Alters Mitochondrial Function in Human Neuron-Like Cells
Ghosh, S., Patel, N., Rahn, D. A., McAllister, J., Sadeghi, S., Horwitz, G., Berry, D., Wang, K. X., & Swerdlow, R. H. (2007) · Molecular Pharmacology · doi:10.1124/mol.106.033845 · Cited by 119 · cited 2×
“We and others previously proposed using brain mitochondrial biogenesis induction to treat AD [133,134].”
BackgroundBone Density and Brain Atrophy in Early Alzheimer's Disease
Loskutova, N., Honea, R. A., Vidoni, E. D., Brooks, W. M., & Burns, J. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1185 · Cited by 118 · cited 1×
“We also found AD subjects have reduced lean (muscle) mass and bone density [116,117,118].”
BackgroundMitochondrial function impairment induced by amyloid β-peptide on PC12 cells
Pereira, C., Santos, M. S., & Oliveira, C. (1998) · NeuroReport · doi:10.1097/00001756-199806010-00015 · Cited by 115
Body Mass Index and Cognitive Decline in Mild Cognitive Impairment
Cronk, B. B., Johnson, D. K., & Burns, J. M. (2010) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3181a6bf3f · Cited by 109 · cited 1×
“We extended this finding by showing body composition and cognitive decline rates correlate; MCI subjects with low body mass index (BMI) values progress more rapidly than those with high BMI values [119].”
BackgroundReduced gray matter volume in normal adults with a maternal family history of Alzheimer disease
Honea, R. A., Swerdlow, R. H., Vidoni, E. D., Goodwin, J., & Burns, J. M. (2010) · Neurology · doi:10.1212/wnl.0b013e3181c918cb · Cited by 106 · cited 1×
“We recently used VBM to analyze MRI scans from non-demented elderly individuals reporting FHm, FHp, and FH- AD family histories [45].”
MethodCybrids in Alzheimer's disease: A cellular model of the disease?
Schon, E. A., Shoubridge, E. A., & Moraes, C. T. (1998) · Neurology · doi:10.1212/wnl.51.1.326 · Cited by 101 · cited 3×
“Azide-mediated cytochrome oxidase inhibition increases free radical production [69], and oxygen radical production is increased in AD cybrid cell lines with reduced cytochrome oxidase Vmax activities [24, 70].”
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
Reduced Limbic and Hypothalamic Volumes Correlate with Bone Density in Early Alzheimer's Disease
Loskutova, N., Honea, R. A., Brooks, W. M., & Burns, J. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1364 · Cited by 93
Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells
Gasparini, L., Racchi, M., Benussi, L., Curti, D., Binetti, G., Bianchetti, A., Trabucchi, M., & Govoni, S. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00536-3 · Cited by 89 · cited 1×
“Treating cells with sodium azide, a cytochrome oxidase inhibitor, shifts AβPP processing to an amyloidogenic derivative [63,64].”
BackgroundMitochondrial Gene Therapy Augments Mitochondrial Physiology in a Parkinson's Disease Cell Model
Keeney, P. M., Quigley, C. K., Dunham, L. D., Papageorge, C. M., Iyer, S., Thomas, R. R., Schwarz, K. M., Trimmer, P. A., Khan, S. M., Portell, F. R., et al. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.023 · Cited by 88 · cited 1×
“To this end we are developing a chimeric recombinant human transcription factor A (rhTFAM) protein that can transduce cell plasma and mitochondrial membranes, bind mtDNA, and activate both mtDNA expression and replication [137].”
BackgroundBekris, L. M., Millard, S. P., Galloway, N. M., Vuletic, S., Albers, J. J., Li, G., Galasko, D. R., DeCarli, C., Farlow, M. R., Clark, C. M., et al. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-13303 · Cited by 85 · cited 1×
“This association may arise via effects on APOE expression, or may exist independent of APOE [102,103,104].”
BackgroundSzabados, T., Dul, C., Majtényi, K., Hargitai, J., Pénzes, Z., & Urbanics, R. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.01.016 · Cited by 84 · cited 1×
“Tau phosphorylation increases in rats and cultured neurons exposed to ETC inhibitors [60,61,62].”
BackgroundTreating neurodegeneration by modifying mitochondria: potential solutions to a “complex” problem
Swerdlow, R. H. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1676 · Cited by 81 · cited 1×
“Our hypothesis predicts therapies that enhance neuron aerobic metabolism may benefit late-onset AD patients [129,130].”
BackgroundFamily patterns of coronary heart disease mortality: The Framingham Longevity Study
Brand, F. N., Kiely, D. K., Kannel, W. B., & Myers, R. H. (1992) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(92)90009-c · Cited by 81 · cited 1×
“One large epidemiology study found that while maternal and paternal longevity both influence an individual’s life expectancy, maternal longevity has a greater impact [96, 97].”
BackgroundAssociation of parental dementia with cognitive and brain MRI measures in middle-aged adults
Debette, S., Wolf, P. A., Beiser, A., Au, R., Himali, J. J., Pikula, A., Auerbach, S. H., DeCarli, C. S., & Seshadri, S. S. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67833 · Cited by 77
Cardiorespiratory Fitness in Early-stage Alzheimer Disease
Burns, J. M., Mayo, M. S., Anderson, H. S., Smith, H. J., & Donnelly, J. E. (2008) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31815a9ddc · Cited by 65 · cited 1×
“We determined peak oxygen consumption (VO 2 ) in an AD subject cohort [123].”
BackgroundBekris, L. M., Galloway, N. M., Montine, T. J., Schellenberg, G. D., & Yu, C. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30993 · Cited by 63 · cited 1×
“This association may arise via effects on APOE expression, or may exist independent of APOE [102,103,104].”
BackgroundYamaguchi, H., Yamazaki, T., Ishiguro, K., Shoji, M., Nakazato, Y., & Hirai, S. (1992) · Acta Neuropathologica · doi:10.1007/bf00304629 · Cited by 55
Tauists, Baptists, Syners, Apostates, and new data
Trojanowski, J. Q. (2002) · Annals of Neurology · doi:10.1002/ana.10281 · Cited by 53 · cited 1×
“Tau, prion, and environmental causes have all been proposed to initiate AD and mediate progression [11,12,13].”
BackgroundMitochondria‐derived oxidative stress induces a heat shock protein response
Barrett, M. J., Alones, V., Wang, K. X., Phan, L., & Swerdlow, R. H. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20249 · Cited by 51 · cited 1×
“Azide-mediated cytochrome oxidase inhibition increases free radical production [69], and oxygen radical production is increased in AD cybrid cell lines with reduced cytochrome oxidase Vmax activities [24, 70].”
BackgroundHamblet, N. S., & Castora, F. J. (1997) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00158-9 · Cited by 44 · cited 1×
“Relative to age-matched control brains, mtDNA deletion levels are elevated in AD subject brains [53,54].”
BackgroundCell and animal models of mtDNA biology: progress and prospects
Khan, S. M., Smigrodzki, R. M., & Swerdlow, R. H. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00224.2006 · Cited by 43 · cited 1×
“We have also proposed the enhancement of mitochondrial gene expression to treat AD [136].”
BackgroundMitochondrial medicine and the neurodegenerative mitochondriopathies
Swerdlow, R. H. (2009) · Pharmaceuticals · doi:10.3390/ph2030150 · Cited by 43 · cited 1×
“Our hypothesis predicts therapies that enhance neuron aerobic metabolism may benefit late-onset AD patients [129,130].”
BackgroundAlzheimer's Disease and Transmissible Virus Dementia (Creutzfeldt‐Jakob Disease)
BROWN, P., SALAZAR, A. M., GIBBS, C. J., & GAJDUSEK, D. C. (1982) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1982.tb26849.x · Cited by 43 · cited 1×
“Tau, prion, and environmental causes have all been proposed to initiate AD and mediate progression [11,12,13].”
BackgroundThe Outcome of Elderly Patients with Cognitive Complaints but Normal Neuropsychological Tests
Nunes, T., Fragata, I., Ribeiro, F., Palma, T., Marôco, J. P., Cannas, J., Secca, M. F., Menezes, C. M., Carmo, I., Cunha, G., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1210 · Cited by 42 · cited 1×
“Similarly, cognitive complaints that are unaccompanied by signs (subjective cognitive impairment; SCI) may portend an increased AD risk [29].”
BackgroundBrown, A. M., Sheu, R. K.-F., Mohs, R., Haroutunian, V., & Blass, J. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:16:1:41 · Cited by 40 · cited 1×
“els of retrievable, intact mtDNA are reduced in AD brains [58,59].”
BackgroundPolymorphic variation in cytochrome oxidase subunit genes
Lu, J., Wang, K., Rodova, M., Esteves, R., Berry, D., E, L., Crafter, A., Barrett, M., Cardoso, S. M., Onyango, I., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100123 · Cited by 33 · cited 2×
“synonymous mtDNA COX gene substitution [49].”
BackgroundApolipoprotein E and Alzheimer's disease: signal transduction mechanisms
Strittmatter, W. J. (2001) · Biochemical Society Symposia · doi:10.1042/bss0670101 · Cited by 30 · cited 1×
“Apolipoprotein E protein has been shown to influence Aβ trafficking and cell signal transduction, either of which could affect Aβ toxicity [100,101].”
BackgroundAmyloid imaging of alzheimer’s disease using pittsburgh compound B
Johnson, K. A. (2006) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-006-0052-5 · Cited by 25 · cited 1×
“Pittsburgh Compound B (PIB) is a PET ligand that binds brain amyloid deposits [46].”
BackgroundRegulation of Alzheimer ß-Amyloid Precursor Trafficking and Metabolism
Gandy, S., & Petanceska, S. S. (2001) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-1249-3_7 · Cited by 16 · cited 1×
“Apolipoprotein E protein has been shown to influence Aβ trafficking and cell signal transduction, either of which could affect Aβ toxicity [96,97].”
BackgroundHypotheses Concerning the Aetiology of Alzheimer's Disease
Tolédano, A. (1988) · Pharmacopsychiatry · doi:10.1055/s-2007-1017060 · Cited by 14
Homotaurine: A failed drug for Alzheimer’s disease and now a nutraceutical for memory protection
Swanoski, M. T. (2009) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp080576 · Cited by 12
Prevalence of dementia after age 90: Results from The 90+ Study
Corrada, M. M., Brookmeyer, R., Berlau, D., Paganini-Hill, A., & Kawas, C. H. (2008) · Neurology · doi:10.1212/01.wnl.0000310773.65918.cd · Cited by 11
If we live long enough, will we all be demented?
Hogan, D. B. (2008) · Neurology · doi:10.1212/01.wnl.0000319660.82871.17 · Cited by 7
Price (1999) · doi:10.1002/1531-8249(199903)45:3
Flagged first, then by citations
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
Cited by
Sorted by citations
Oxidative Stress: A Key Modulator in Neurodegenerative Diseases
Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019) · Molecules · doi:10.3390/molecules24081583 · Cited by 2,398
Mitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850
Self-citationMitochondrial Dysfunction in Neurodegenerative Diseases
Johri, A., & Beal, M. F. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.192138 · Cited by 806
“It has been proposed that in sporadic AD mitochondrial dysfunction is the primary event that causes A deposition, synaptic degeneration, and formation of neurofibrillary tangles (Swerdlow et al., 2010).”
BackgroundThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786
“This review will discuss recent AD biomarker data, diagnostic criteria, and clinical trial results from the perspective of a different AD hypothesis, the “mitochondrial cascade hypothesis” [21-27].”
BackgroundCalkins, M. J., Manczak, M., Mao, P., Shirendeb, U., & Reddy, P. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr381 · Cited by 646
“AD is also associated with inflammatory responses, synaptic damage and mitochondrial structural and functional abnormalities (3-10).”
Background
Metadata
- Authors
- Swerdlow, R. H., Burns, J. M., & Khan, S. M.
- Affiliations
- University of Kansas (US)
- Gencia (United States) (US)
- Corresponding author
- Swerdlow, Russell H.
- 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
- 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
- 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.
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