The DOI matches its Crossref record; 67 of the 70 references it cites were found in a registry or an index.
Aβ Oligomers Cause Localized Ca 2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines
Open accessAbstract
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.
Overview
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
Cites
Statistics
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Ab oligomers also cause tau mislocalization (77,78).”
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 1×
“We also note that in our preparations we did not consistently observe a band at 56 kDa, a species that has been reported to be toxic for transgenic mice (Lesné et al., 2006) but can be visualized in certain conditions (Walsh et al., 2005; Ashe, 2006; Bernstein et al., 2009).”
BackgroundRetractedSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · cited 1×
“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
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064 · cited 1×
“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.”
BackgroundDiffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · cited 3×
“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
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · cited 1×
“These include loss of synapses and neurons, deficiency in neurotransmitters and metabolism, aggregation of amyloid- (A )-peptides into extracellular “amyloid plaques” and Tau protein into intracellular “neurofibrillary tangles” (Selkoe, 2004; Binder et al., 2005; Ballatore et al., 2007).”
BackgroundReducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · cited 1×
“…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).”
BackgroundTransmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803
Physiology and Pathophysiology of Purinergic Neurotransmission
Burnstock, G. (2007) · Physiological Reviews · doi:10.1152/physrev.00043.2006 · Cited by 1,609 · cited 1×
“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.,…”
Background
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
Cited by
Sorted by citations
Items 501–593 of 593
Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review
Mitsuyama, F., Futatsugi, Y., Okuya, M., Kawase, T., Karagiozov, K. L., Kato, Y., Kanno, T., Sano, H., Nagao, S., & Koide, T. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/519682 · Cited by 5
Amyloid β Hypothesis in the Development of Therapeutic Agents for Alzheimer’s Disease
Adeniji, A. O., Adams, P. W., & Mody, V. V. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802810-0.00007-6 · Cited by 7
Immunotherapy and Biomarkers in Neurodegenerative Disorders
Ingelsson, M., & Lannfelt, L. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-3560-4 · Cited by 6
Oxidative stress induces tau hyperphosphorylation via MARK activation in neuroblastoma N1E-115 cells
Liu, Y., Chen, Y., & Fukui, K. (2023) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.22-39 · Cited by 7
Ahmed, G. A.-R., Khalil, S., hotaby, W. E., Abbas, L., Farrag, A. R. H., AbdEl-Aal, W. E., Sherif, H. H. A., Abdel‐Rahman, E. A., Saber, S. H., Hassan, M. A. E., et al. (2020) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2020.104931 · Cited by 6
Li, Y., Zheng, W. H., Wuyun, Q., Cao, S., Ruan, J., & Zhang, Y. (2018) · BioMed Research International · doi:10.1155/2018/5486403 · Cited by 5
Neuroimmune Dynamics in Alzheimer’s Disease Progression
Andrade, V., Guzmán‐Martínez, L., Vergara-Pulgar, K., & Maccioni, R. B. (2017) · InTech eBooks · doi:10.5772/intechopen.68941 · Cited by 4
Bitan, F. R. A. G. (2014) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9781608058525114020014 · Cited by 4
“ Induce τ phosphorylation [177] and misfolding [183].”
BackgroundAllen, H., Allawh, R., Cusack, C., & Joshi, S. (2018) · Journal of Neuroinfectious Diseases · doi:10.4172/2314-7326.1000276 · Cited by 5
“This production from the microbes is very likely a major source of βAPP when the cells lyse (after the disintegration of the dendrites) and the material becomes extracellular [10,11].”
BackgroundNeurotoxic Ca2+ Signaling Induced by Amyloid-β Oligomers in Aged Hippocampal Neurons In Vitro.
Núñez, L., Calvo-Rodriguez, M., Caballero, E., García-Durillo, M., & Villalobos, C. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7816-8_20 · Cited by 5
From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer’s Disease Landscape
Bougea, A. M., Debasa‐Mouce, M., Gulkarov, S., Castro‐Mosquera, M., Reiss, A. B., & Ouro, A. (2025) · Medicina · doi:10.3390/medicina61081462 · Cited by 5
Mark4 ablation attenuates pathological phenotypes in a mouse model of tauopathy
Sultanakhmetov, G., Limlingan, S. J. M., Fukuchi, A., Tsuda, K., Suzuki, H., Kato, I., Saito, T., Weitemier, A. Z., & Ando, K. (2024) · Brain Communications · doi:10.1093/braincomms/fcae136 · Cited by 5
“11 Tau phosphorylation at Ser262 and Ser356 affects its interactions with chaperone complexes and degradation, 12,13 intracellular distribution, 14 and liquid–liquid phase separation.”
BackgroundAubrey, L. D., Lutter, L., Fennell, K., Purton, T., Ward, N. L., Serpell, L., & Xue, W.-F. (2023) · bioRxiv · doi:10.1101/2023.07.14.549001 · Cited by 4
The pathway to Alzheimer′s disease
Allawh, H. B. A. R., & Joshi, S. (2017) · doi:10.4172/2155-9597-c1-040 · Cited by 4
Mavroeidi, P., Mavrofrydi, O., Pappa, E., Panopoulou, M., Papazafiri, P., Haralambous, S., & Efthimiopoulos, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170157 · Cited by 4
“have provided evidence that A treatment resulted in increased tau phosphorylation at residues Ser202/Thr205 and Ser262/Ser356 in dendritic regions [12].”
BackgroundVillemagne, V. L., Okamura, N., & Rowe, C. C. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.05.001 · Cited by 7
Zhao, W., Toolan, D. M., Hepler, R. W., Wolfe, A. L., Yu, Y., Price, E. A., Uebele, V. N., Schachter, J. B., Reynolds, I. J., Renger, J. J., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102022 · Cited by 4
Neurotransmitter receptors in Alzheimer's disease
Lombardero, L., Llorente-Ovejero, A., Manuel, I., & Rodríguez-Puertas, R. (2020) · doi:10.1016/b978-0-12-815868-5.00028-1 · Cited by 4
Prospects and Challenges for Alzheimer Therapeutics
Wolfe, M. S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00023-x · Cited by 5
Yang, T., Ay, Y. A., Kaur, S., Butler, R. R., Tran, K. C., Liu, H., Langness, V. F., Massa, S. M., & Longo, F. M. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02263-5 · Cited by 3
“All signaling pathway components were assessed following 1 h of treat-ment, and changes in pTau (using AT8 and pTau217 antibodies) were assessed following 3 h of treatment, as these changes are fairly rapid [92, 96].”
Cobalt(III) Schiff Base complexes stabilize non-fibrillar amyloid-β aggregates with reduced toxicity
Roberts, K. F., Brue, C. R., Preston, A., Baxter, D., Herzog, E., Varelas, E., & Meade, T. J. (2020) · bioRxiv · doi:10.1101/2020.05.12.091405 · Cited by 3
“Disruptions in tau processing are common to many neurodegenerative disorders and, in the case of AD, generally believed to be downstream of Aβ toxicity.(2-6) The precise mechanism by which these pathological changes induce synaptic dysfunction and neurodegeneration remains unknown.”
BackgroundMolecular Pathways in Alzheimer’s Disease and Cognitive Function
Chen, X., Reichert, M. C., & Gan, L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802851-3.00005-x · Cited by 3
Abdelaziz, A. M., Shokr, M. M., Fathy, M. K., & Fawzy, M. N. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02531-y · Cited by 2
“Similarly, pathological forms of tau, which may also be present in astrocytes in AD, disrupt microtubule integrity (Zempel et al. 2010 ).”
Weber, A. J., Ng, B., Greathouse, K. M., Bennett, D. A. A., Tasaki, S., Gaiteri, C., & Herskowitz, J. H. (2026) · Neuron · doi:10.1016/j.neuron.2026.03.001 · Cited by 3
The aggregation of amyloid-β: from condensation, nucleation, and conformation to targeting therapy
Chen, B., Chen, T., Sun, Z., Liu, L., Jia, Y., Ji, Y., Wang, J., Sun, F., & Huang, Y. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124397 · Cited by 2
Shoff, T. A., Derbez-Morin, M., Cai, P., & Julian, R. R. (2026) · PNAS Nexus · doi:10.1093/pnasnexus/pgag034 · Cited by 4
“For example, high A β levels lead to the delocalization of tau within neurons and increase distribution into the somatodendritic compartment (55).”
Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer’s Disease
Gasca-Martínez, Y., Ontiveros‐Torres, M. Á., López-Gallegos, I., & Jarero-Basulto, J. J. (2026) · Pathophysiology · doi:10.3390/pathophysiology33010014 · Cited by 2
“During AD progression, the dynamics and stability of microtubules are altered both directly and indirectly by the presence of A β Os, as demonstrated by multiple studies [97,98].”
Exploring cannabinoid modulation on autophagy mechanisms in Alzheimer’s disease: a review
Ntsapi, C., Weyers, M., Chinheya, R. M., Jim, T., & Matsabisa, M. G. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1748368 · Cited by 2
Bell‐Simons, M., Breuer, H., Wunderlich, L., Chmes, H., Adam, D., Klimek, J., Buchholz, S., & Zempel, H. (2025) · Aging Cell · doi:10.1111/acel.70215 · Cited by 2
“Hyperphosphorylation of AT8 and KXGS residues is associated with Tau missorting and aggregation in AD (Bancher et al. 1989; Mercken et al. 1992; Zempel and Mandelkow 2014; Zempel et al. 2010).”
Self-citationIdentification of TMED10 as A Regulator for Neuronal Exocytosis of Amyloid Beta 42
Meng, P., Sha, L., Yu, X., Wang, Y., Zhang, E., Meng, K., Li, B., Zhao, Q., & Xu, Q. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01492-3 · Cited by 2
Wang, X., Dai, L., Wu, N., Wu, D., Wang, X., Meng, X., Zhang, Q., Lu, J., Yan, X., Zhang, J., et al. (2025) · MedComm · doi:10.1002/mco2.70156 · Cited by 1
“Over the past decade, strong evidence has emerged that A β oligomers can cause tau pathology, synaptic dysfunction, neuronal loss, and cognitive impairment [1, 2].”
Kanuri, S. H. (2024) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-024-00853-5 · Cited by 2
“This anatomical redistribution of tau incites signaling events including enhanced NMDA [N-methyl-D aspartate] receptor activity, calcium excitotoxicity, tau phosphorylation and microtubule destruction in the dendrites [42].”
BackgroundMustafa, I., Awad, A. A. R., Fgaier, H., Mansur, A., & Elkamel, A. (2020) · Computers and Chemical Engineering · doi:10.1016/j.compchemeng.2020.107165 · Cited by 2
Miguel, L., Frébourg, T., Campion, D., & Lecourtois, M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-190906 · Cited by 2
Zhu, J.-Z., Fu, Q.-X., Xia, C., & Ma, G.-Z. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4457 · Cited by 2
Alzheimer Disease and Dementia
AYDIN, A. C. (2020) · Journal of Literature Pharmacy Sciences · doi:10.5336/pharmsci.2019-71813 · Cited by 3
Konrad, K. D., Paradise, V., Demir, L. Y., Nguyen, C., Makinson, C. D., Ming, Z., & Ramachandran, K. V. (2026) · Nature Neuroscience · doi:10.1038/s41593-026-02398-7 · Cited by 3
“However, multiple groups have shown that endogenous wild-type tau protein is present in the dendrites at much lower expression levels compared with the axon 17,22–28 and that newly synthesized tau protein can be upregulated in neuronal dendrites by various stimuli 17,18,26,29 .”
Chai, J.-Y., Zhang, Y. P., Zhang, Z., Ma, D., Cao, Y.-H., Zhu, S.-R., Yun-zhi, M., Luo, L.-L., Zhan, Y.-L., Fan, Z.-Y., et al. (2026) · Reviews in the Neurosciences · doi:10.1515/revneuro-2026-0041 · Cited by 3
“These kinases act on Ser/Thr sites of tau protein, leading to its hyperphosphorylation (Zempel et al. 2010).”
Monoclonal antibodies and small molecules: on the cutting edge of Alzheimer’s disease therapy
Ouro, A., Ben-Dor, G. A., Debasa‐Mouce, M., Gulkarov, S., Leon, J. D., Castro‐Mosquera, M., Sobrino, T., Bougea, A. M., & Reiss, A. B. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1766762 · Cited by 1
“Several studies argue that the increase of expression or activity of Ser/Thr kinases such as GSK3 β or Cyclin-dependent kinase 5 (Cdk5) decreases the expression of Protein Phosphatase 1 (PP1) and 2A (PP2A), which are phosphatases whose function is to dephosphorylate Tau (Sontag et al., 1996; Gong et al., 1993).”
InfluentialMendoza-Franco, G., Rodríguez‐Cruz, F., Estrada-Modesto, S., González, E. O. H., Boucard, A. A., Ríos, M. A. M., Basurto‐Islas, G., & García‐Sierra, F. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261422415 · Cited by 1
“16 21 Other abnormalities that occur in AD include the aberrant accumulation of misfolded proteins and failure in their transport and degradation.”
Feng, N.-N., Li, L., Liu, L.-Z., He, R.-B., Xian, X., Liu, L.-R., Hu, Y.-Y., & Li, W. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110600 · Cited by 1
Gupta, S., Kishore, A., Rishi, V., & Aggarwal, A. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05045-7 · Cited by 1
“Localization of Tau in spines is evidently observed and immensely reported [132, 133], and in several tauopa-thy including AD, Tau phosphorylation or oligimerization has been reported to disrupt the microtubule dynamics rendering spine loss [134, 135].”
Galeotti, A. A., Santucci, L., Klimek, J., Kabbani, M. A. A., Zempel, H., & Raffa, V. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1519628 · Cited by 2
Self-citationLi, S., Wang, Y., Liang, X., & Li, Y. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877241307403
Chen, A., Shea, D. W., & Daggett, V. (2024) · Scientific Reports · doi:10.1038/s41598-024-57107-w · Cited by 1
Bazan, N. G., Bhattacharjee, S., Kala-Bhattacharjee, S., Ledet, A. J., & Mukherjee, P. K. (2023) · Research Square · doi:10.21203/rs.3.rs-3185942/v1 · Cited by 1
Deep tissue imaging with multiphoton microscopy in the short-wavelength infrared windows
Bourdakos, K., Xu, L., Crisford, A., Xu, D., Abughazaleh, I., Johnson, P., Cook, H., Srisamran, P., Oreffo, R., Richardson, D., et al. (2023) · Photonex · doi:10.1117/12.2647553 · Cited by 1
“SHG has been used as a neuroimaging modality to investigate neurodegenerative disorders including Alzheimer’s disease and glaucoma in which damage or breakdown of axonal microtubules is involved 14, 15 .”
Oba, T., Saito, T., Asada, A., Shimizu, S., Iijima, K., & Ando, K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.20.107284 · Cited by 1
Glennon, E. B., Lau, D. H. W., Gabriele, R. M. C., Taylor, M. F., Troakes, C., Elliott, C., Killick, R., Hanger, D., Perez-Nievas, B., & Noble, W. (2019) · bioRxiv · doi:10.1101/646406 · Cited by 1
“This is an important concept since alterations in the trafficking and normal positioning of tau are considered to be early pathogenic changes in AD (53-57).”
BackgroundPickett, E. K., Herrmann, A. G., McQueen, J., Abt, K. M., Dando, O., Tulloch, J., Jain, P., Dunnett, S. L., Sohrabi, S., Fjeldstad, M. P., et al. (2018) · SSRN Electronic Journal · doi:10.1101/393405 · Cited by 2
“…idea both from work showing that lowering tau levels protects against Aβ mediated synaptic plasticity deficits and from studies indicating that dendritic tau mediates Aβ synaptotoxicity (Ittner et al., 2010; Roberson et al., 2011; Roberson et al., 2007; Shipton et al., 2011; Zempel et al., 2010).”
BackgroundNevado-Holgado, A., Ribe, E. M., Thei, L., Furlong, L., Angel-Mayer, M., Quan, J., Richardson, J., Cavanagh, J., & Lovestone, S. (2017) · bioRxiv · doi:10.1101/179267 · Cited by 1
Musardo, S. (2016) · doi:10.13130/s-musardo_phd2016-01-11 · Cited by 1
“Moreover, hippocampal primary neurons exposed to Aβ oligomers show an evident missorting of endogenous tau into the somatodendritic compartment (Zempel et al 2010).”
BackgroundRôle des ADAM dans le processus physiopathologique de la maladie d'Alzheimer
Laumet, G. O. (2010) · theses.fr (ABES) · doi:10.70675/94126786zf990z488ezb471z5f1d5686766c
Mondragón‐Rodríguez, S., Perry, G. L., & Peña‐Ortega, F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802810-0.00008-8 · Cited by 2
Neurochemical Aspects of Alzheimer Disease
Farooqui, A. A. (2016) · Springer eBooks · doi:10.1007/978-3-319-15889-1_1 · Cited by 2
Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease
Zetterberg, H., & Schott, J. M. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-3560-4_11 · Cited by 5
Alzheimer’s Disease and Mechanism-Based Attempts to Enhance Cognition
Draffin, J. E., Knafo, S., & Heneka, M. T. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-417042-1.00009-7 · Cited by 1
Alzheimer’s Disease and Other Neurodegenerative Disorders
Rosén, C., Zetterberg, H., & Blennow, K. (2015) · Springer eBooks · doi:10.1007/978-3-319-01225-4_20 · Cited by 2
Kasai, A. (2010) · Journal of The Society of Japanese Women Scientists · doi:10.5939/sjws.10007 · Cited by 1
“Amyloid beta and hyperphosphorylated Tau protein are now considered to be important, independent causative molecules in Alzheimer’s disease (Huang and Jiang 2009, Zempel et al. 2010).”
BackgroundAstrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice
Raulin, A.-C., Alnobani, A., Rodriguez-Martinez, P., Lee, E., Linares, C., Yslas, A. R., Li, M., Ren, Y., Doss, S. V., Roy, B., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04002-9
Wang, H., Fan, X., Ping, J., Shao, Q., Cai, W., Wang, H., Ji, Q., Su, M., & Qian, W. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00590-0
“Calcium-dependent kinase networks drive the abnormal phosphorylation of tau, causing tau to mislocalize to dendrites where it abnormally recruits Fyn to postsynaptic receptors [2, 6, 23, 119].”
Yang, T., Tran, K. C., Leng, A., Langness, V. F., Massa, S. M., & Longo, F. M. (2026) · Cells · doi:10.3390/cells15191822
“After 21 days in vitro (DIV), murine neurons acquire an adult-like phenotype with respect to neuronal polarity, spine formation, and microtubule and neurofilament cytoskeletal architecture [76,77].”
TUBB4B mRNA in CSF and plasma exosomes as a biomarker for tracking Alzheimer's disease progression
Yang, X., Gao, S., & Wang, P.-C. (2026) · Journal of Radiation Research and Applied Sciences · doi:10.1016/j.jrras.2026.102555
Aβ-induced CaMKII hyperactivation is associated with impaired lysosomal maturation and mitophagy
Suh, E. C., Kim, Y. A., Lee, K. E., & Park, E. (2026) · Neurochemistry International · doi:10.1016/j.neuint.2026.106252
Tkemaladze, J. (2026) · Longevity Horizon · doi:10.65649/9347j1ap · Cited by 2
Kabbani, M. A. A., Köhler, L., Wied, T., Adam, D., Klimek, J., & Zempel, H. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18081038 · Cited by 1
Self-citationAtzori, M., Fabbretti, E., Ciraci, V., Zucchelli, S., Bon, C., Mikašinović, S., Baj, G., Gustincich, S., & Tongiorgi, E. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06175-4
“Aβ oligomer challenge and mis-sorting of endogenous Tau into the somatodendritic compartment are initial events of AD leading to a depletion of spines and breakdown of microtubules in dendrites [ 49–51 ].”
García-Carlos, C. A., Salas-Gallardo, A., González-Pereyra, P., Basurto‐Islas, G., Perry, G., & Mondragón‐Rodríguez, S. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261417377
“33,34 In this regard, we and others have reported that A β is responsible for increasing tau phosphorylation close to the MDr sites.”
Kim, J. P., Lee, H., Kim, B., Nho, K. T., Risacher, S. L., Saykin, A. J., Seo, S. W., & Kim, H. (2025) · Dementia and Neurocognitive Disorders · doi:10.12779/dnd.2025.24.4.246
“31-38 Various forms of A β , including fibrillar, 31,33 oligomeric, 32,35,37 and dimeric 34 forms, have consistently elevated phosphorylated tau levels.”
Konrad-Vicario, K., Paradise, V., Demir, L., Makinson, C., Ming, Z., & Ramachandran, K. (2025) · bioRxiv · doi:10.1101/2025.06.04.657939
Schneeweis, A. K., & Pak, D. T. S. (2023) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2023.106475 · Cited by 1
Proteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric AßPreprint
Matafora, V., Gorb, A., Noble, W., Bachi, A., Perez-Nievas, B., & Jimenez-Sanchez, M. (2023) · bioRxiv · doi:10.1101/2023.01.18.523916
Dávila-Bouziguet, E., Casòliba-Melich, A., Targa-Fabra, G., Galera-López, L., Ozaita, A., Maldonado, R., Delgado-García, J., Gruart, A., Ávila, J., Soriano, E., et al. (2020) · bioRxiv · doi:10.1101/2020.12.10.417907
Rahman, M. A., Hossain, S., Abdullah, N., & Aminudin, N. (2020) · doi:10.21203/rs.3.rs-104135/v1
Vityala, Y. (2020) · Indian Journal of Forensic Medicine & Toxicology · doi:10.37506/ijfmt.v14i2.2759
Alzheimer’s Disease: Future Efforts to Thwart Memory Loss
Allen, H. (2019) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2019.22.003738
“The Abeta, which is produced at the same time as the biofilms, interacts with tau protein and converts it to p-tau [10,11].”
BackgroundThe Link Between Diabetes, Glucose Control, and Alzheimer's Disease and Neurodegenerative Diseases
Verdile, G., Fraser, P. E., & Martins, R. N. (2019) · Wiley eBooks · doi:10.1002/9781119356752.ch4
Neuroimmunological phenomena involved in chronic traumatic brain injury
Velasco‐González, R., Vargas‐Castro, N., Mendoza-Negrete, K., Acacio‐Martínez, D., Luna‐Mendoza, J., Méndez-Cuesta, L. A., Sotomayor-Sobrino, M. A., Ochoa-Aguilar, A., & Acevedo, C. G. (2019) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12492 · Cited by 1
Caractérisation d'anticorps à domaine unique dirigés contre la protéine Tau
Danis, C. (2018) · theses.fr (ABES) · doi:10.70675/c783a062zb57bz4024z85d0z509baaed8a1b
“In pathological condition, where Tau is found hyperphosphorylated, Tau is detached 217 from microtubules and can diffuse to the somatodendritic compartment (Zempel et al. 2010, 201).”
BackgroundReduce the Risk of Dementia; Early Diagnosis of Alzheimer’s Disease
Jakhmola, S., & Jha, H. C. (2018) · Advances in intelligent systems and computing · doi:10.1007/978-981-13-0923-6_53 · Cited by 1
Stability and folding of G-protein coupled receptors associated to degenerative diseases
Dong, X. (2016) · UPCommons institutional repository (Universitat Politècnica de Catalunya) · doi:10.5821/dissertation-2117-96351
Faucher, P. (2015) · theses.fr (ABES) · doi:10.70675/32388e8eze91bz48c8z8d7fzbc873b067cfd
“De plus, plusieurs travaux ont mis en évidence que les oligomères d’Aβ(1-42) jouent un rôle dans l’activation de la protéine GSK3β impliquée dans la phosphorylation pathologique de la protéine tau (Tomiyana et al., 2010 ; Zempel et al., 2010).”
BackgroundFrandemiche, M. (2013) · theses.fr (ABES) · doi:10.70675/260ed9c4zd958z47e0za418z0f324a1b102b
“Deux études menées par Zempel et collaborateurs sur des cultures primaires de neurones montrent que les oligomères d’Aβo induisent une augmentation de la phosphorylation de tau, mais aussi une délocalisation dendritique importante et une déstabilisation des microtubules (Zempel et al., 2010; 2013).”
Interaction du peptide beta amyloïde avec les membranes plasmiques cellulaires
Gilson, V. (2013) · theses.fr (ABES) · doi:10.70675/5a91d188zfbf8z47efza16bza77cebf6c54f
Novielli, C. (2010) · Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · doi:10.13130/novielli-chiara_phd2010-12-20
Tau-Centric Therapies for Treating Alzheimer’s Disease
Quraishe, S., Cowan, C. M., & Mudher, A. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803690-7.00005-3 · Cited by 1
Neurochemical Aspects of β-Amyloid Cascade Hypothesis for Alzheimer’s Disease
Farooqui, A. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809937-7.00001-x · Cited by 1
Perspective, Summary, and Directions for Future Research on Alzheimer’s Disease
Farooqui, A. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809937-7.00010-0
Fluid Biomarkers and Diagnostics
Zetterberg, H., & Blennow, K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802173-6.00021-6
Knuesel, I. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800228-5.00004-2
Linking Molecular Neurobiology to Therapeutic Approaches for Alzheimer’s Disease with PET
Luiten, P. G. M., Masman, M. F., Dobos, N., Nyakas, C. J., de Vries, E. F. J., Dierckx, R., & Eisel, U. L. M. (2014) · Springer eBooks · doi:10.1007/978-3-642-54307-4_20
Zhang, S.-T. (2013) · cIRcle (University of British Columbia) · doi:10.14288/1.0074224
“…increased tau phosphorylation, disturbance in Ca2+ hemostasis, NMDARindependent cytotoxicity in primary neurons and cognitive impairment in mice (Walsh et al., 2002, Hoshi et al., 2003, Cleary et al., 2005b, Demuro et al., 2005, Lesne et al., 2006, Shankar et al., 2008a, Zempel et al., 2010).”
BackgroundEntrada de calcio inducida por los oligómeros del péptido amiloide en la Enfermedad de Alzheimer
Ortega, E. C. (2013) · UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) · doi:10.35376/10324/3786 · Cited by 1
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
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
