Tau oligomerization: a role for tau aggregation intermediates linked to neurodegeneration
Abstract
Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and frontotemporal dementia with Parkinsonism linked to chromosome 17, all known collectively as tauopathies. Tau protein is a member of microtubule (MT)-associated proteins. Tau is a highly soluble and natively unfolded protein dominated by a random coil structure in solution. It is believed that aberrant modifications of tau, including phosphorylation, truncation, and conformational changes, induce filamentous aggregation. However, the mechanism underlying the conversion of tau protein from a soluble state to one of insoluble aggregates still remains elusive. The importance of tau aggregation intermediates (e.g. tau dimer, tau multimer, and granular tau oligomer) in disease pathogenesis was suggested by recent studies. Here, we review the latest developments in tracking the structural changes of tau protein and discuss the utility improving our understanding of tau aggregation pathway leading to human tauopathies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 neurodegeneration observed in these models reflects toxicity of soluble, non-aggregated forms of tau, and may recapitulate early stages of the abnormal metabolism and toxicity of tau.
“suggesting that the neurodegeneration observed in these models reflects toxicity of soluble, non-aggregated forms of tau, and may recapitulate early stages of the abnormal metabolism and toxicity of tau [11–14].”
Cites
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · see citing works
Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., & Crowther, R. A. (1996) · Nature · doi:10.1038/383550a0 · Cited by 1,036 · see citing works
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Tau filament formation in transgenic mice expressing P301L tau
Götz, J., Chen, F., Barmettler, R., & Nitsch, R. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006531200 · Cited by 495 · see citing works
Toward a unified scheme for the aggregation of tau into Alzheimer paired helical filaments
Barghorn, S., & Mandelkow, E. (2002) · Biochemistry · doi:10.1021/bi026469j · Cited by 341 · see citing works
Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90063-w · Cited by 332 · see citing works
PHF and PHF-like fibrils –cause or consequence?
Ihara, Y. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00200-1 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A. C., Alvarez, V. E., Lee, N. C. Y., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277061 · Cited by 985 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
Self-citationSydow, A., Van der Jeugd, A., Zheng, F., Ahmed, T., Balschun, D., Petrova, O., Drexler, D., Zhou, L., Rune, G., Mandelkow, E., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5245-10.2011 · Cited by 302 · see citing works
Recent advances in our understanding of neurodegeneration
Jellinger, K. A. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0240-y · Cited by 274 · see citing works
Takeuchi, H., Iba, M., Inoue, H., Higuchi, M., Takao, K., Tsukita, K., Karatsu, Y., Iwamoto, Y., Miyakawa, T., Suhara, T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021050 · Cited by 247 · see citing works
Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., & LaFerla, F. M. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.02.012 · Cited by 210 · see citing works
Tau 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 · see citing works
Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau
Van der Jeugd, A., Hochgräfe, K., Ahmed, T., Decker, J. M., Sydow, A., Hofmann, A., Wu, D., Messing, L., Balschun, D., D’Hooge, R., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0987-3 · Cited by 135 · see citing works
Ando, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
Golde, T. E., & Miller, V. M. (2009) · Alzheimer's Research & Therapy · doi:10.1186/alzrt5 · Cited by 98 · see citing works
- Authors
- Sahara, N., Maeda, S., & Takashima, A.
- Affiliations
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Maeda, S.
- Takashima, A.
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2008-12-01
- Volume
- 5
- Issue
- 6
- Pages
- 591-598
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W2155683552
- Cited by
- 99
- References
- 8
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 4 · 2012: 12
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- RIKEN Brain Science Institute
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- tau protein, tau oligomerization, tauopathy, neurodegeneration, Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, frontotemporal dementia with parkinsonism linked to chromosome 17, tau phosphorylation, tau truncation, protein conformational change, microtubule-associated proteins, aggregation pathways
- MeSH terms
- Alzheimer Disease, Animals, Humans, Phosphorylation, Protein Conformation, Amyloid beta-Peptides, tau Proteins, Microscopy, Atomic Force, Neurodegenerative Diseases
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
