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Aβ Oligomers Cause Localized Ca 2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines
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Aggregation of amyloid-β (Aβ) and Tau protein are hallmarks of Alzheimer's disease (AD), and according to the Aβ-cascade hypothesis, Aβ is considered toxic for neurons and Tau a downstream target of Aβ. We have investigated differentiated primary hippocampal neurons for early localized changes following exposure to Aβ oligomers. Initial events become evident by missorting of endogenous Tau into the somatodendritic compartment, in contrast to axonal sorting in normal neurons. In missorted dendritic regions there is a depletion of spines and local increase in Ca 2+ , and breakdown of microtubules. Tau in these regions shows elevated phosphorylation at certain sites diagnostic of AD-Tau (e.g., epitope of antibody 12E8, whose phosphorylation causes detachment of Tau from microtubules, and AT8 epitope), and local elevation of certain kinase activities (e.g., MARK/par-1, BRSK/SADK, p70S6K, cdk5, but not GSK3β, JNK, MAPK). These local effects occur without global changes in Tau, tubulin, or kinase levels. Somatodendritic missorting occurs not only with Tau, but also with other axonal proteins such as neurofilaments, and correlates with pronounced depletion of microtubules and mitochondria. The Aβ-induced effects on microtubule and mitochondria depletion, Tau missorting, and loss of spines are prevented by taxol, indicating that Aβ-induced microtubule destabilization and corresponding traffic defects are key factors in incipient degeneration. By contrast, the rise in Ca 2+ levels, kinase activities, and Tau phosphorylation cannot be prevented by taxol. Incipient and local changes similar to those of Aβ oligomers can be evoked by cell stressors (e.g., H 2 O 2 , glutamate, serum deprivation), suggesting some common mechanism of signaling.
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“mis-localization to dendrites and spines causing neurotoxicity [52]”
From Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice (2026) · cites this paper as [52]
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“Under normal conditions, tau is primarily localized to axons and promotes formation and stabilization of microtubules; however, in AD, tau becomes hyperphosphorylated and mislocalizes to somatodendritic compartments (Avila et al., 2004, Ittner et al., 2010, Zempel et al., 2010).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Zempel et al., 2010
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“the activities of two major tau kinases, GSK3 and PAR-1/microtubule affinity-regulating kinases (MARKs), are often associated with tau detachment from microtubules and Aβ-induced augmentation of tau toxicity [37, 39, 43–45].”
From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [39]
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“Notably, studies in cultured neurons and transgenic Drosophila showed that Aβ-induced augmentation of tau toxicity caused by Aβ depends on tau phosphorylation at these sites [39, 45, 56–58].”
From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [39]
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“Aβ promotes tau phosphorylation at disease-associated sites in in vitro and in vivo models of AD [2, 35–41].”
From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [39]
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“In cellular and animal models, co-expression of Aβ augments tau phosphorylation at these sites and increases the levels of active GSK3 and PAR-1/MARK [2, 35–41, 43, 44].”
From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [39]
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“Ab oligomers also cause tau mislocalization (77,78).”
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“Under normal conditions, tau is primarily localized to axons and promotes formation and stabilization of microtubules; however, in AD, tau becomes hyperphosphorylated and mislocalizes to somatodendritic compartments (Avila et al., 2004, Ittner et al., 2010, Zempel et al., 2010).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Zempel et al., 2010
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“Despite numerous studies on the pathway of APP misprocessing and its consequences for neurons the modes of A toxicity have remained enigmatic (Haass and Selkoe, 2007; Small and Duff, 2008).”
BackgroundCommon structure of soluble amyloid oligomers implies common mechanism of pathogenesis
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“Nevertheless, there were differences in structure because dot blots with antibody A11, which recognizes a more toxic generic amyloid conformation (Kayed et al., 2003), were more intense for F12 medium than for Nb (Fig.”
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“There is a moderate decrease of ATP which is more apparent with F12 than with Nb medium, suggesting that F12, which was used in the original procedure (Lambert et al., 1998), could have some toxic effects on its own.”
BackgroundMethodTau-mediated neurodegeneration in Alzheimer’s disease and related disorders
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“…conversely Tau is considered necessary for the progression of neurodegeneration, as seen in cell and animal models (Rapoport et al., 2002; King et al., 2006; Roberson et al., 2007), and indeed the Tau pathology correlates well with clinical symptoms (Braak and Braak, 1991; Clavaguera et al., 2009).”
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“We also tested extracellular ATP (100 M, 3 h), which functions as a stress signal and induces Ca 2 influx via P2 receptors and has been implicated in neurodegenerative disease (Burnstock, 2007).”
MethodShankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592 · cited 1×
“4e,f), and involving NMDA receptors and others (De Felice et al., 2007; Shankar et al., 2007).”
BackgroundThe axonal transport of mitochondria
Saxton, W. M., & Hollenbeck, P. J. (2012) · Journal of Cell Science · doi:10.1242/jcs.053850 · Cited by 1,218 · cited 1×
“As shown previously (Stamer et al., 2002; Hollenbeck and Saxton, 2005; Thies and Mandelkow, 2007), such mitochondrial traffic jams cause a local drop of energy (ATP) and consequently spine destruction through the perturbation of the actin network and loss of synaptic components (Whiteman et al.,…”
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Research works printed but not linked: 3
- 10.1242/jcs.02745 · DOI · Paper page
- 10.1074/jbc.R800036200 · DOI
- 10.1186/1750-1326-4-48 · DOI · Paper page
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“Zempel and collaborators have shown that AβOs induce tau missorting, a phenomenon in which axonal taumoves to dendrites in hyperphosphorylated form, disrupting cytoskeletal organization and axonal transport (Zempel et al., 2010), ultimately instigating neuronal collapse.”
BackgroundSoluble Aβ oligomer production and toxicity
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“The activity-dependent transport mechanism into spines may be altered in anti- and pro-aggregant animals because of TauRD missorting to somatodendritic compartments (Zempel et al., 2010).”
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“Similarly, exposure to oligomeric Ab promotes levels of tau in dendrites (Figure 2B, e), contributing to the increased levels of tau in this compartment in AD (Zempel et al., 2010).”
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“…when neurons suffer from various neurotoxic insults, such as Aβ (Otth et al., 2002; Han et al., 2005; Zheng et al., 2005, 2010; Lopes et al., 2007; Zempel et al., 2010; Shukla et al., 2012), ischemia/hypoxia (Wen et al., 2007; Barros-Miñones et al., 2013), oxidative stress (Absalon et al.,…”
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“These include increased phosphorylation and cytoplasmic and dendritic translocation, often linked to neurodegeneration which was Tau or even P-Tau dependent [26-38].”
BackgroundLost after translation: missorting of Tau protein and consequences for Alzheimer disease
Zempel, H., & Mandelkow�, E. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.004 · Cited by 284
Self-citationMondragón-Rodríguez, S., Trillaud-Doppia, E., Dudilot, A., Bourgeois, C., Lauzon, M., Leclerc, N., & Boehm, J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.401240 · Cited by 272
Protein phosphorylation in neurodegeneration: friend or foe?
Tenreiro, S., Eckermann, K., & Outeiro, T. F. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00042 · Cited by 252
“Therefore, MARKs may have regulatory functions in spine morphology and synaptic transmission, but may also act as critical mediators in Aβ-induced toxicity on synapses and dendritic spines (Zempel et al., 2010; Hayashi et al., 2011; Yu et al., 2012).”
BackgroundPathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242
Larson, M. E., Sherman, M. A., Amar, F., Nuvolone, M., Schneider, J. A., Bennett, D. A., Aguzzi, A., & Lesné, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1858-12.2012 · Cited by 290
“Following this initial report, several in vivo lines of evidence demonstrated that A , Fyn, and tau might constitute a deleterious triad in AD physiopathology (Chin et al., 2004, 2005; Ittner et al., 2010; Zempel et al., 2010; Roberson et al., 2011).”
BackgroundInfluentialRetractedThe Role of Cdk5 in Alzheimer’s Disease
Liu, S., Wang, C., Jiang, T., Tan, L., Xing, A., & Yu, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9369-x · Cited by 274
“kinases, and finally, leading to neuronal loss [51, 52].”
BackgroundSoluble forms of tau are toxic in Alzheimer's disease
Kopeikina, K., Hyman, B., & Spires-Jones, T. (2012) · Translational Neuroscience · doi:10.2478/s13380-012-0032-y · Cited by 232
“Two families of protein kinases contribute to tau phosphorylation, those that are proline directed and tend to phosphorylate serine and threonine motifs outside the microtubule binding domain and those that are KXGS-motif and non-proline directed and tend to phosphorylate within the repeat domain [14, 31].”
InfluentialFluid biomarkers in Alzheimer’s disease – current concepts
Rosén, C., Hansson, O., Blennow, K., & Zetterberg, H. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-20 · Cited by 221
“They can inhibit hippocampal long-term potentiation in vivo [87], and cause abnormal tau phosphorylation and neuritic dystrophy [88-90].”
Ochalek, A., Mihalik, B., Avci, H. X., Chandrasekaran, A., Téglási, A., Bock, I., Giudice, M. L., Táncos, Z., Molnár, K., László, L., et al. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0317-z · Cited by 225
Tau in neurodegenerative disease
Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.23 · Cited by 222
“In neurons which were acutely exposed to Aβ, Aβ initiated tau-mediated neurotoxicity by facilitating tau phosphorylation (60) and directing pathogenic tau species into dendritic spines (33), leading to spine collapse and dendritic degeneration.”
BackgroundSanchez-Varo, R., Trujillo-Estrada, L., Sanchez-Mejias, E., Torres, M., Baglietto-Vargas, D., Moreno-Gonzalez, I., De Castro, V., Jimenez, S., Ruano, D., Vizuete, M., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0896-x · Cited by 222
“Supporting the possible involvement of microtubule destabilization in AD pathogenesis, it has been recently reported [31] that natural oligomeric Ab, isolated from AD patients, disrupted the microtubule cytoskeleton and caused neuritic dystrophy (see also [67]).”
BackgroundCdk5: a multifaceted kinase in neurodegenerative diseases
Cheung, Z. H., & Ip, N. Y. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.11.003 · Cited by 233
Hong, S., Ostaszewski, B. L., Yang, T., O’Malley, T. T., Jin, M., Yanagisawa, K., Li, S., Bartels, T., & Selkoe, D. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.027 · Cited by 213
Endoplasmic Reticulum Ca2+ Handling in Excitable Cells in Health and Disease
Stutzmann, G. E., & Mattson, M. P. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003814 · Cited by 255
Amyloid-Dependent and Amyloid-Independent Stages of Alzheimer Disease
Hyman, B. T. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.70 · Cited by 194
Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration
Li, X., Kumar, Y., Zempel, H., Mandelkow, E., Biernat, J., & Mandelkow, E. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.376 · Cited by 232
“The barrier breaks down when Tau is phosphorylated in its repeat domain and detached from microtubules, for example, by the kinase MARK/Par1.”
BackgroundInfluentialSelf-citationA role for tau at the synapse in Alzheimer’s disease pathogenesis
Pooler, A. M., Noble, W., & Hanger, D. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.018 · Cited by 203
“Cultured rat neurons treated with oligomeric Ab also displayed translocation of tau from the axonal compartment to dendrites with concurrent increase of tau phosphorylation at specific epitopes (Zempel et al., 2010).”
BackgroundChen, L.-L., Fan, Y.-G., Zhao, L.-X., Zhang, Q., & Wang, Z.-Y. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106301 · Cited by 200
Goure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt272 · Cited by 190
Caspase-2 cleavage of tau reversibly impairs memory
Zhao, X., Kotilinek, L. A., Smith, B., Hlynialuk, C., Zahs, K., Ramsden, M., Cleary, J., & Ashe, K. H. (2016) · Nature Medicine · doi:10.1038/nm.4199 · Cited by 187
Atypical, non-standard functions of the microtubule associated Tau protein
Sotiropoulos, I., Galas, M., Silva, J. M., Skoulakis, E. M. C., Wegmann, S., Maina, M. B., Blum, D. L., Sayas, C. L., Mandelkow, E., Mandelkow�, E., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0489-6 · Cited by 221
Self-citationUntangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease
Pereira, J. B., Janelidze, S., Ossenkoppele, R., Kvartsberg, H., Brinkmalm, A., Mattsson, N., Stomrud, E., Smith, R. A., Zetterberg, H., Blennow, K., et al. (2020) · Brain · doi:10.1093/brain/awaa395 · Cited by 208
“Although the associations revealed by these data are cross-sectional, the most likely interpretation based on previous animal studies (Zempel et al., 2010, 2013; Rozkalne et al., 2011; Cohen et al., 2013; Spires-Jones and Hyman, 2014; Koffie et al., 2019), is that amyloid-b deposition is followed…”
BackgroundResultPickett, E. K., Herrmann, A. G., McQueen, J., Abt, K., Dando, O., Tulloch, J., Jain, P., Dunnett, S., Sohrabi, S., Fjeldstad, M. P., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.044 · Cited by 179
“…Ab-mediated synaptic plasticity deficits, from studies indicating that dendritic tau mediates Ab synaptotoxicity, and from a study that found synaptic tau phosphorylation in APP/PS1 mice (Roberson et al., 2007, 2011; Shipton et al., 2011; Ittner et al., 2010; Zempel et al., 2010; Wu et al., 2018).”
BackgroundCrimins, J. L., Pooler, A. M., Polydoro, M., Luebke, J. I., & Spires‐Jones, T. L. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.03.002 · Cited by 173
Thornton, C., Bright, N. J., Sastre, M., Muckett, P. J., & Carling, D. (2011) · Biochemical Journal · doi:10.1042/bj20101485 · Cited by 193
Mitochondrial Dysfunction: a Potential Therapeutic Target to Treat Alzheimer’s Disease
Nand, S., Singh, C., Singh, A., Singh, M. P., & Singh, S. P. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01945-y · Cited by 215
Aβ-induced Golgi fragmentation in Alzheimer’s disease enhances Aβ production
Joshi, G., Chi, Y., Huang, Z.-P., & Wang, Y.-Z. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1320192111 · Cited by 169
“It has been proposed that Aβ can trigger Ca influx (23), which activates calpain, a Ca-dependent protease that cleaves p35 to produce p25 for cdk5 activation (24).”
BackgroundTau Oligomers: The Toxic Player at Synapses in Alzheimer’s Disease
Guerrero-Muñoz, M. J., Gerson, J., & Castillo-Carranza, D. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00464 · Cited by 168
“…it is possible that a direct interaction between the two proteins may be involved in the induction of synaptic dysfunction as tau and Aβ coexist within synaptic compartments in AD brain (Hoover et al., 2010; Ittner et al., 2010; Zempel et al., 2010; Tai et al., 2012; Miller et al., 2014).”
BackgroundTau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β
Vossel, K. A., Xu, J. C., Fomenko, V., Miyamoto, T., Suberbielle, E., Knox, J. A., Ho, K., Kim, D. H., Yu, G.-Q., & Mucke, L. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201407065 · Cited by 167
“Tau has been implicated in A-induced cytoskeletal changes (King et al., 2006; Zempel et al., 2013), including deacetylation and polyglutamylation of tubulin and microtubule disassembly within dendrites of subpopulations of neurons (Zempel et al., 2010, 2013).”
Degradation of tau protein by autophagy and proteasomal pathways
Wang, Y., & Mandelkow, E. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120071 · Cited by 166
Self-citationSynaptic pathology: A shared mechanism in neurological disease
Henstridge, C. M., Pickett, E. K., & Spires‐Jones, T. L. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.005 · Cited by 176
“Treating primary neurons with physiological concentrations of amyloid-β induces synapse loss, which has recently been associated with tau mislocalization to dendrites [62].”
Sohn, P. D., Tracy, T. E., Son, H.-I., Zhou, Y., Leite, R. E. P., Miller, B. L., Seeley, W. W., Grinberg, L. T., & Gan, L. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0109-0 · Cited by 160
Role of Aβ in Alzheimer’s-related synaptic dysfunction
Zhang, H., Jiang, X., Ma, L., Wei, W., Li, Z., Chang, S., Wen, J., Sun, J., & Li, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.964075 · Cited by 157
Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Hernandez, C., Barrett, A. D. T., Dineley, K., & Kayed, R. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.4989-14.2015 · Cited by 149
“Moreover, this redistribution of tau seems to be responsible for spine loss (Zempel et al., 2010).”
BackgroundHuman neural stem cells alleviate Alzheimer-like pathology in a mouse model
Lee, I.-S., Jung, K., Kim, I., Lee, H.-J., Kim, M., Yun, S., Hwang, K., Shin, J. E., & Park, K. I. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0035-6 · Cited by 170
“Alternatively, the small decrease in Aβ levels observed in the present study may have affected levels of phosphorylated tau because Aβ directly precedes aberrant tau phosphorylation [54–56].”
Braak, H., & Del Tredici, K. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhy152 · Cited by 148
Tammineni, P., Ye, X., Feng, T., Aikal, D., & Cai, Q. (2017) · eLife · doi:10.7554/elife.21776 · Cited by 175
“…the association of Ab oligomers with AVs in AD brains, we utilized the well-characterized A11 antibody that only recognizes soluble Ab oligomers, but not APP and its cleaved products C99, soluble monomer, or insoluble fibrils (Jimenez et al., 2008, 2011; Kayed et al., 2003; Zempel et al., 2010).”
MethodReduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model
Lasagna‐Reeves, C. A., de Haro, M., Hao, S., Park, J., Rousseaux, M. W. C., Al‐Ramahi, I., Jafar‐Nejad, P., Vilanova-Velez, L., See, L., Maio, A. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.022 · Cited by 154
Bukke, V. N., Archana, M., Villani, R., Romano, A. D., Wawrzyniak, A., Balawender, K., Orkisz, S., Beggiato, S., Serviddio, G., & Cassano, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207452 · Cited by 161
The Toxicity and Polymorphism of β-Amyloid Oligomers
Huang, Y., & Liu, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124477 · Cited by 176
Iijima-Ando, K., Sekiya, M., Maruko-Otake, A., Ohtake, Y., Suzuki, E., Lu, B., & Iijima, K. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002918 · Cited by 142
“The reduction in mitochondria in the axon may be due to alterations in mitochondrial fission/fusion [3,5,6] and/or due to defects in the axonal transport of mitochondria [4,6,8,10–12].”
BackgroundTau protein is essential for stress-induced brain pathology
Lopes, S., Vaz‐Silva, J., Pinto, V., Dalla, C., Kokras, N., Bedenk, B. T., Mack, N., Czisch, M., Almeida, O. F. X., Sousa, N., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600953113 · Cited by 147
“Although Tau is found mainly in the neuronal axon and soma, previous work suggests that Tau is missorted and accumulated at synapses under pathological conditions (24, 28).”
BackgroundResultMillan, M. J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.03.004 · Cited by 151
Ardiles, Á. O., Tapia‐Rojas, C., Mandal, M., Alexandre, F., Kirkwood, A., Inestrosa, N. C., & Palacios, A. G. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201209109 · Cited by 152
Metadata
- Authors
- Zempel, H., Thies, E., Mandelkow, E., & Mandelkow, E.-M.
- Affiliations
- Max Planck Unit for Structural Molecular Biology (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Mandelkow, Eva-Maria
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-09-08
- Volume
- 30
- Issue
- 36
- Pages
- 11938-11950
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6633549
- OpenAlex
- W2041956586
- Cited by
- 686
- References
- 70
- Citations by year
- 2026: 29 · 2025: 33 · 2024: 27 · 2023: 22 · 2022: 30 · 2021: 38 · 2020: 54 · 2019: 46 · 2018: 49 · 2017: 46 · 2016: 50 · 2015: 51 · 2014: 61 · 2013: 54 · 2012: 50
- FWCI
- 32.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta oligomers, Alzheimer's disease, tau phosphorylation, dendrites, microtubule destabilization, dendritic spines, neurofilaments, mitochondria, paclitaxel, p70S6K, cyclin-dependent kinase 5, hippocampal neurons, axonal transport, oxidative stress, glutamate, serum deprivation
- MeSH terms
- Adenosine Triphosphate, Analysis of Variance, Animals, Calcium, Cells, Cultured, Dendrites, Embryo, Mammalian, Hippocampus, L-Lactate Dehydrogenase, Microtubules, Mitochondria, Neurons, Peptide Fragments, Phosphorylation, Protein Kinases, Time Factors, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins, Rats, Sprague-Dawley, Protein Transport, Microscopy, Electron, Transmission, Dendritic Spines, Rats
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