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Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis
Open accessAbstract
One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads to a decrease in RNA translation. The aberrant tau-ribosome association also impaired synthesis of the synaptic protein PSD-95, suggesting that this phenomenon contributes to synaptic dysfunction. These findings provide novel information about tau-protein interactions in human brains, and they describe, for the first time, a dysfunctional consequence of tau-ribosome associations that directly alters protein synthesis. Significance statement: Despite the identification of abnormal tau-ribosomal interactions in tauopathies >25 years ago, the consequences of this association remained elusive until now. Here, we show that pathological tau associates closely with ribosomes in AD brains, and that this interaction impairs protein synthesis. The overall result is a stark reduction of nascent proteins, including those that participate in synaptic plasticity, which is crucial for learning and memory. These data mechanistically link a common pathologic sign, such as the appearance of pathological tau inside brain cells, with cognitive impairments evident in virtually all tauopathies.
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“m6A is known to accumulate in the cytoplasm in response to stress, but the function of cytoplasmic m6A remains to be clearly delineated (Meier et al., 2016; Briggs et al., 2017; Koren et al., 2019; Ries et al., 2019; Wolozin and Ivanov, 2019; Fu and Zhuang, 2020).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Meier et al., 2016
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Cites
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
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
Harding, H. P., Zhang, Y., & Ron, D. (1999) · Nature · doi:10.1038/16729 · Cited by 3,310
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014
SUnSET, a nonradioactive method to monitor protein synthesis
Schmidt, E. K., Clavarino, G., Ceppi, M., & Pierre, P. (2009) · Nature Methods · doi:10.1038/nmeth.1314 · Cited by 1,706
Migaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G. M., Morrison, J. H., et al. (1998) · Nature · doi:10.1038/24790 · Cited by 1,160
2014 Alzheimer's disease facts and figures
Alzheimer's Association (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2014.02.001 · Cited by 1,064
Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles
Guo, J. L., & Lee, V. M.-Y. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209296 · Cited by 636
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Clos, A. L., Jackson, G. R., & Kayed, R. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-39 · Cited by 633
Sustained translational repression by eIF2α-P mediates prion neurodegeneration
Moreno, J. A., Radford, H. E., Peretti, D., Steinert, J. R., Verity, N., Martin, M. G., Halliday, M., Morgan, J., Dinsdale, D. D., Ortori, C. A., et al. (2012) · Nature · doi:10.1038/nature11058 · Cited by 616
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Rissman, R. A., Poon, W. W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M. P., LaFerla, F. M., Rohn, T. T., & Cotman, C. W. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420640 · Cited by 543
Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau.
Greenberg, S. G., Davies, P., Schein, J., & Binder, L. I. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48531-6 · Cited by 542
Rosso, S. M. (2003) · Brain · doi:10.1093/brain/awg204 · Cited by 508
Clark, L. N., Poorkaj, P., Wszolek, Z., Geschwind, D., Nasreddine, Z. S., Miller, B. L., Li, D., Payami, H., Awert, F., Markopoulou, K., et al. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.22.13103 · Cited by 488
Ribosome Dysfunction Is an Early Event in Alzheimer's Disease
Ding, Q., Markesbery, W. R., Chen, Q., Li, F., & Keller, J. N. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3040-05.2005 · Cited by 433
Rizzu, P., Swieten, J. C. V., Joosse, M., Hasegawa, M., Stevens, M., Tibben, A., Niermeijer, M. F., Hillebrand, M., Ravid, R., Oostra, B. A., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302256 · Cited by 432
Phosphorylation determines two distinct species of tau in the central nervous system
Papasozomenos, S. C., & Binder, L. I. (1987) · Cell Motility · doi:10.1002/cm.970080303 · Cited by 420
Barghorn, S., Zheng‐Fischhöfer, Q., Ackmann, M., Biernat, J., von Bergen�, M., Mandelkow�, E., & Mandelkow�, E. (2000) · Biochemistry · doi:10.1021/bi000850r · Cited by 351
Abisambra, J. F., Jinwal, U. K., Blair, L. J., O’Leary, J. C., Li, Q., Brady, S., Wang, L., Guidi, C., Zhang, B., Nordhues, B. A., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5397-12.2013 · Cited by 275
Self-citationContrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies
Vanderweyde, T. E., Yu, W. H., Varnum, M. M., Liu‐Yesucevitz, L., Citro, A., Ikezu, T., Duff, K., & Wolozin, B. L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1592-12.2012 · Cited by 235
Self-citationMarciniak, S. J., García‐Bonilla, L., Hu, J., Harding, H. P., & Ron, D. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200508099 · Cited by 183
Duvarci, S., Nader, K., & LeDoux, J. E. (2008) · Learning & Memory · doi:10.1101/lm.1027208 · Cited by 130
Pathological stress granules in Alzheimer’s disease
Ash, P. E. A., Vanderweyde, T. E., Youmans, K. L., Apicco, D. J., & Wolozin, B. (2014) · Brain Research · doi:10.1016/j.brainres.2014.05.052 · Cited by 129
Self-citationAbisambra, J. F., Jinwal, U. K., Miyata, Y., Rogers, J. T., Blair, L. J., Li, X., Seguin, S. P., Wang, L., Jin, Y. L., Bacon, J. A., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.027 · Cited by 110
Self-citationActivation of the hepatic LDL receptor promoter by thyroid hormone.
Lopez, D., Abisambra Socarrás, J. F., Bedi, M., & Ness, G. C. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.05.001 · Cited by 109
Self-citationThe Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy
Zhang, C., Xing, A., Tan, M., Tan, L., & Yu, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9415-8 · Cited by 98
Meier, S. E., Bell, M. C., Lyons, D. N., Ingram, A., Chen, J., Gensel, J. C., Zhu, H., Nelson, P. T., & Abisambra, J. F. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150298 · Cited by 84
Self-citationJones, J. R., Lebar, M. D., Jinwal, U. K., Abisambra, J. F., Koren, J., Blair, L. J., O’Leary, J. C., Davey, Z. S., Trotter, J. H., Johnson, A. G., et al. (2010) · Journal of Natural Products · doi:10.1021/np100572z · Cited by 78
Self-citationCdc37/Hsp90 Protein Complex Disruption Triggers an Autophagic Clearance Cascade for TDP-43 Protein
Jinwal, U. K., Abisambra, J. F., Zhang, J., Dharia, S. P., O’Leary, J. C., Patel, T., Braswell, K., Jani, T., Gestwicki, J. E., & Dickey, C. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.367268 · Cited by 77
Self-citationClinical and pathological features of an Alzheimer's disease patient with the MAPT ΔK280 mutation
Momeni, P., Pittman, A. M., Lashley, T., Vandrovcová, J., Malzer, E., Luk, C. Y., Hulette, C., Lees, A. J., Révész, T., Hardy, J., et al. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.07.013 · Cited by 69
DnaJA1 Antagonizes Constitutive Hsp70-Mediated Stabilization of Tau
Abisambra, J. F., Jinwal, U. K., Suntharalingam, A., Arulselvam, K., Brady, S., Cockman, M. E., Jin, Y., Zhang, B., & Dickey, C. A. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.02.003 · Cited by 68
Self-citationCerebellar cortical tau pathology in progressive supranuclear palsy and corticobasal degeneration
Piao, Y.-S., Hayashi, S., Wakabayashi, K., Kakita, A., Aida, I., Yamada, M., & Takahashi, H. (2002) · Acta Neuropathologica · doi:10.1007/s00401-001-0488-2 · Cited by 49
Abisambra, J. F., Fiorelli, T., Padmanabhan, J., Neame, P., Wefes, I., & Potter, H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008556 · Cited by 42
Self-citationAlz-50 immunohistochemistry in the normal sheep striatum: a light and electron microscope study
Nelson, P. T., Marton, L. S., & Saper, C. B. (1993) · Brain Research · doi:10.1016/0006-8993(93)91385-6 · Cited by 33
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Tracy, T. E., Madero‐Pérez, J., Swaney, D. L., Chang, T. S., Moritz, M., Konràd, C., Ward, M. E., Stevenson, E. J., Hüttenhain, R., Kauwe, G., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.041 · Cited by 355
A walk through tau therapeutic strategies
Jadhav, S., Ávila, J., Schöll, M., Kovács, G. G., Kövari, E., Škrabana, R., Evans, L., Kontseková, E., Malawska, B., de Silva, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0664-z · Cited by 299
Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo
Apicco, D. J., Ash, P. E. A., Maziuk, B., LeBlang, C., Medalla, M., Al Abdullatif, A., Ferragud, A., Botelho, E., Ballance, H. I., Dhawan, U., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0022-z · Cited by 281
“Somatodendritic mislocalization would allow tau to interact with RBPs, RNA, and ribosomes, which provides a mechanism through which tau can inhibit protein synthesis 40 .”
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Lester, E., Ooi, F. K., Bakkar, N., Ayers, J. I., Woerman, A. L., Wheeler, J., Bowser, R. P., Carlson, G. A., Prusiner, S. B., & Parker, R. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.026 · Cited by 212
Metadata
- Authors
- Meier, S., Bell, M., Lyons, D. N., Rodriguez-Rivera, J., Ingram, A., Fontaine, S. N., Mechas, E., Chen, J., Wolozin, B., LeVine, H., Zhu, H., & Abisambra, J. F.
- Affiliations
- Boston University (US)
- University of Kentucky (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-01-20
- Volume
- 36
- Issue
- 3
- Pages
- 1001-1007
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4719006
- OpenAlex
- W2287813183
- Cited by
- 190
- References
- 35
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 13 · 2023: 16 · 2022: 23 · 2021: 28 · 2020: 24 · 2019: 23 · 2018: 8 · 2017: 11 · 2016: 5
- FWCI
- 12.62
- 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)
- UKnowledge (University of Kentucky) (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense (AZ140097)
- Alzheimer's Association (NIRG-14-322441)
- GlaxoSmithKline
- University of Kentucky (P30 AG028383, AG028383, P30 CA177558)
- National Institutes of Health (AG028 383, NIH/NIMHD L32 MD009205-01, UL1TR000117, L32 MD009205-01, NIH/NINDS 1R01 NS091329-01)
- National Institute on Aging (AG-028383, P30AG028383, NIA P30 AG028383, NIH/NIA P30 AG028383)
- National Cancer Institute (P30CA177558)
- National Institute of General Medical Sciences (P30GM110787, P20GM103486)
- National Institute of Neurological Disorders and Stroke (NS091329, R01NS091329, R01NS077284, P30NS051220)
- National Center for Research Resources (S10RR029127)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (L32MD009205-01, L32 MD009205)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- pathological tau, Alzheimer's disease, tauopathy, protein synthesis, endoplasmic reticulum, PSD-95, synaptic dysfunction, memory loss, synaptic plasticity
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Brain, Cells, Cultured, Female, Humans, Male, Microsomes, Neurons, Ribosomes, Protein Biosynthesis, tau Proteins, Tauopathies
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