Selective Phosphorylation of Adult Tau Isoforms in Mature Hippocampal Neurons Exposed to Fibrillar Aβ
Abstract
How senile plaques and neurofibrillary tangles are linked represents a major gap in our understanding of the pathophysiology of Alzheimer's disease. We characterized a hippocampal neuronal culture system in which tau undergoes maturation in vivo; rat neurons maintained in culture for more than 3 weeks replicated the splicing and phosphorylation changes that tau undergoes upon maturation in situ. Using this model system, we induced an Alzheimer-like neuritic dystrophy following the application of fibrillar beta-amyloid. The dystrophy consisted of focal distortions and swellings within the neurites and an altered phosphorylation of the adult tau isoforms. Fibrillar beta-amyloid induced the concomitant activation of MAP kinase and GSK3 beta. The aberrant activation of several signaling pathways may lead to the abnormal phosphorylation of tau and neuritic degeneration.
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?
Aβ promotes tau phosphorylation at disease-associated sites in in vitro and in vivo models of AD.
“Aβ promotes tau phosphorylation at disease-associated sites in in vitro and in vivo models of AD [2, 35–41].”
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.
“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].”
Cites
Goedert, M., & Jakes, R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07870.x · Cited by 929 · see citing works
Paudel, H. K., Lew, J., Ali, Z., & Wang, J. H. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49492-1 · Cited by 285 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · see citing works
Tau is essential to β-amyloid-induced neurotoxicity
Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., & Ferreira, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092136199 · Cited by 807 · see citing works
Self-citationGSK3 and tau: Two convergence points in Alzheimer’s disease
Hernandez, F., Lucas, J. J., & Avila, J. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-129025 · Cited by 359 · see citing works
Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology
Tesseur, I., Zou, K., Esposito, L., Bard, F., Berber, E., Can, J. V., Lin, A. H., Crews, L., Tremblay, P., Mathews, P., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27341 · Cited by 355 · see citing works
Zheng, W.-H., Bastianetto, S., Mennicken, F., Ma, W., & Kar, S. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00404-9 · Cited by 321 · see citing works
Park, S.-Y., & Ferreira, A. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1125-05.2005 · Cited by 262 · see citing works
Self-citationModels of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism
Stancu, I.-C., Vasconcelos, B., Terwel, D., & Dewachter, I. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-51 · Cited by 256 · see citing works
The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice
Moretti, R., & Caruso, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010231 · Cited by 248 · see citing works
Pei, J.-J., Braak, H., An, W.-L., Winblad, B., Cowburn, R. F., Iqbal, K., & Grundke-Iqbal, I. (2002) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00488-6 · Cited by 247 · see citing works
Knowles, J. K., Rajadas, J., Nguyen, T.-V. V., Yang, T., LeMieux, M. C., Vander Griend, L., Ishikawa, C., Massa, S. M., Wyss-Coray, T., & Longo, F. M. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.0620-09.2009 · Cited by 184 · see citing works
Merkwirth, C., Martinelli, P., Korwitz, A., Morbin, M., Brönneke, H. S., Jordan, S. D., Rugarli, E. I., & Langer, T. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003021 · Cited by 162 · see citing works
Tackenberg, C., & Brandt, R. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3590-09.2009 · Cited by 127 · see citing works
Ferreira, A., & Bigio, E. H. (2011) · Molecular Medicine · doi:10.2119/molmed.2010.00220 · Cited by 112 · see citing works
Self-citationc-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice
Cancino, G. I., Perez de Arce, K., Castro, P. U., Toledo, E. M., von Bernhardi, R., & Alvarez, A. R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.07.007 · Cited by 110 · see citing works
Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies
Hanes, J., Zilka, N., Bartkova, M., Caletkova, M., Dobrota, D., & Novak, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05869.x · Cited by 109 · 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
Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons
Kelly, B. L., & Ferreira, A. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.03.047 · Cited by 85 · see citing works
Self-citationSchnurra, I., Bernstein, H.-G., Riederer, P., & Braunewell, K.-H. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0432 · Cited by 76 · see citing works
Neuronal degeneration, synaptic defects, and behavioral abnormalities in tau45-230 transgenic mice
Lang, A. E., Riherd Methner, D. N., & Ferreira, A. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.017 · Cited by 35 · see citing works
Self-citationDaulatzai, M. A. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9528-x · Cited by 12 · see citing works
- Authors
- Ferreira, A., Lu, Q., Orecchio, L., & Kosik, K. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Ferreira, Adriana
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 1997
- Volume
- 9
- Issue
- 3
- Pages
- 220-234
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1985446830
- Cited by
- 178
- References
- 2
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 7
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau phosphorylation, tau isoforms, Alzheimer's disease, hippocampal neurons, neuritic dystrophy, mitogen-activated protein kinase, GSK3β, amyloid plaques, neurofibrillary tangles
- MeSH terms
- Animals, Cells, Cultured, Hippocampus, Immunohistochemistry, Microscopy, Electron, Phosphorylation, Polymerase Chain Reaction, Amyloid beta-Peptides, tau Proteins, 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
