Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-β Pathologies in 3xTg Mice
Open accessAbstract
Amyloid-β (Aβ) and tau pathologies are intertwined in Alzheimer’s disease, and various immunotherapies targeting these hallmarks are in clinical trials. To determine if tau pathology influences Aβ burden and to assess prophylactic benefits, 3xTg and wild-type mice received tau immunization from 2–6 months of age. The mice developed a high IgG titer that was maintained at 22 months of age. Pronounced tau and Aβ pathologies were primarily detected in the subiculum/CA1 region, which was therefore the focus of analysis. The therapy reduced histopathological tau aggregates by 70–74% overall (68% in males and 78–86% in females), compared to 3xTg controls. Likewise, western blot analysis revealed a 41% clearance of soluble tau (38–76% in males and 48% in females) and 42–47% clearance of insoluble tau (47–58% in males and 49% in females) in the immunized mice. Furthermore, Aβ burden was reduced by 84% overall (61% in males and 97% in females). These benefits were associated with reductions in microgliosis and microhemorrhages. In summary, prophylactic tau immunization not only prevents tau pathology but also Aβ deposition and related pathologies in a sustained manner, indicating that tau pathology can promote Aβ deposition, and that a short immunization regimen can have a long-lasting beneficial effect.
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Active tau immunization reduces tau pathology by targeting single or multiple phospho-epitopes, the amino terminus, full-length normal and mutant tau, or aggregated tau.
“Active tau immunization has been shown to reduce tau pathology by targeting single185, 187, 189–193 or multiple194 phospho-epitopes, the amino terminus195, full-length normal and mutant tau196, 197, or aggregated tau198.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [193]
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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 · see citing works
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
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 · see citing works
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194 · see citing works
Billings, L. M., Oddo, S., Green, K. N., McGaugh, J. L., & LaFerla, F. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.040 · Cited by 1,294 · see citing works
Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H., & LaFerla, F. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.003 · Cited by 780 · see citing works
Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · see citing works
Yanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
Trans-cellular Propagation of Tau Aggregation by Fibrillar Species
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.346072 · Cited by 552 · see citing works
Asuni, A. A., Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2361-07.2007 · Cited by 506 · see citing works
Self-citationPassive Immunization with Anti-Tau Antibodies in Two Transgenic Models
Chai, X., Wu, S., Murray, T. K., Kinley, R. D., Cella, C. V., Sims, H., Buckner, N., Hanmer, J. M., Davies, P., O’Neill, M. J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.229633 · Cited by 346 · see citing works
A closed-field intelligence test for rats.
Rabinovitch, M. S., & Rosvold, H. E. (1951) · Canadian Journal of Psychology/Revue Canadienne de Psychologie · doi:10.1037/h0083542 · Cited by 310 · see citing works
Boutajangout, A., Ingadottir, J., Davies, P., & Sigurdsson, E. M. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07337.x · Cited by 306 · see citing works
Self-citationCastillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · see citing works
Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model
Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-10.2010 · Cited by 272 · see citing works
Self-citationTheunis, C., Crespo-Biel, N., Gafner, V., Pihlgren, M., López-Deber, M. P., Reis, P., Hickman, D. T., Adolfsson, O., Chuard, N., Ndao, D. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072301 · Cited by 259 · see citing works
Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B., & Wısnıewskı, T. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61715-4 · Cited by 258 · see citing works
Self-citationA Method of Rating Animal Intelligence
Hebb, D. O., & Williams, K. E. (1946) · The Journal of General Psychology · doi:10.1080/00221309.1946.10544520 · Cited by 250 · see citing works
Kontseková, E., Žilka, N., Kováčech, B., Novák, P., & Novák, M. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt278 · Cited by 248 · see citing works
Tau immunotherapy for Alzheimer's disease
Pedersen, J. T., & Sigurdsson, E. M. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.03.003 · Cited by 247 · see citing works
Self-citationLuo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · see citing works
Collin, L., Bohrmann, B., Göpfert, U., Oroszlan‐Szovik, K., Ozmen, L., & Grüninger, F. (2014) · Brain · doi:10.1093/brain/awu213 · Cited by 203 · see citing works
Congdon, E. E., Gu, J., Sait, H. B. R., & Sigurdsson, E. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.491001 · Cited by 195 · see citing works
Self-citationZommer, N., Sergeant, N., Schraen-Maschke, S., Blum, D., & Buee, L. (2012) · Current Alzheimer Research · doi:10.2174/156720512800492503 · Cited by 193 · see citing works
Tau passive immunization inhibits not only tau but also Aβ pathology
Dai, C., Tung, Y. C., Liu, F., Gong, C., & Iqbal, K. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0227-5 · Cited by 186 · see citing works
Anti‐tau antibody reduces insoluble tau and decreases brain atrophy
Yanamandra, K., Jiang, H., Mahan, T. E., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.176 · Cited by 185 · see citing works
Castillo‐Carranza, D. L., Gerson, J. E., Sengupta, U., Guerrero‐Munoz, M. J., Lasagna‐Reeves, C. A., & Kayed, R. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132477 · Cited by 180 · see citing works
Tauopathy-like Abnormalities and Neurologic Deficits in Mice Immunized With Neuronal Tau Protein
Rosenmann, H., Grigoriadis, N., Karussis, D., Boimel, M., Touloumi, O., Ovadia, H., & Abramsky, O. (2006) · Archives of Neurology · doi:10.1001/archneur.63.10.1459 · Cited by 178 · see citing works
Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.010 · Cited by 174 · see citing works
Gu, J., Congdon, E. E., & Sigurdsson, E. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.494922 · Cited by 163 · see citing works
Self-citationBi, M., Ittner, A., Ke, Y. D., Götz, J., & Ittner, L. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026860 · Cited by 153 · see citing works
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 · see citing works
Sigurdsson, E. M., Knudsen, E., Asuni, A. A., Fitzer‐Attas, C. J., Sage, D., Quartermain, D., Goñi, F., Frangione, B., & Wısnıewskı, T. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1344-04.2004 · Cited by 148 · see citing works
Self-citationTau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity
d’Abramo, C., Acker, C. M., Jimenez, H. T., & Davies, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062402 · Cited by 144 · see citing works
Sankaranarayanan, S., Barten, D. M., Vana, L., Devidze, N., Yang, L., Cadelina, G. W., Hoque, N., DeCarr, L. B., Keenan, S., Lin, A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125614 · Cited by 143 · see citing works
Distinct Therapeutic Mechanisms of Tau Antibodies
Funk, K. E., Mirbaha, H., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.657924 · Cited by 111 · see citing works
Histological Staining of Amyloid and Pre-amyloid Peptides and Proteins in Mouse Tissue
Rajamohamedsait, H. B., & Sigurdsson, E. M. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-551-0_28 · Cited by 98 · see citing works
Self-citationAsuni, A. A., Boutajangout, A., Scholtzova, H., Knudsen, E., Li, Y. S., Quartermain, D., Frangione, B., Wısnıewskı, T., & Sigurdsson, E. M. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05149.x · Cited by 91 · see citing works
Self-citationThe symmetrical maze: An automated closed-field test series for rats
Davenport, J. W., Hagquist, W. W., & Rankin, G. R. (1970) · Behavior Research Methods · doi:10.3758/bf03211017 · Cited by 83 · see citing works
Tau‐targeting passive immunization modulates aspects of pathology in tau transgenic mice
Ittner, A., Bertz, J., Suh, L. S., Stevens, C. H., Götz, J., & Ittner, L. M. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12821 · Cited by 81 · see citing works
Sigurdsson, E. M., Lee, J. M., Dong, X.-W., Hejna, M. J., & Lorens, S. A. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00154-1 · Cited by 79 · see citing works
Self-citationPassive immunotherapy of tauopathy targeting pSer413‐tau: a pilot study in mice
Umeda, T., Eguchi, H., Kunori, Y., Matsumoto, Y., Taniguchi, T., Mori, H., & Tomiyama, T. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.171 · Cited by 73 · see citing works
Krishnamurthy, P., Deng, Y., & Sigurdsson, E. M. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00059 · Cited by 71 · see citing works
Self-citationLiu, W., Zhao, L., Blackman, B. A., Parmar, M. S., Wong, M. Y., Woo, T., Yu, F., Chiuchiolo, M. J., Sondhi, D., Kaminsky, S. M., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2016-16.2016 · Cited by 68 · see citing works
Repeated immunization of mice with phosphorylated-tau peptides causes neuroinflammation
Rozenstein-Tsalkovich, L., Grigoriadis, N., Lourbopoulos, A., Nousiopoulou, E., Kassis, I., Abramsky, O., Karussis, D., & Rosenmann, H. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.07.006 · Cited by 66 · see citing works
Congdon, E. E., Lin, Y., Rajamohamedsait, H. B., Shamir, D. B., Krishnaswamy, S., Rajamohamedsait, W. J., Rasool, S., González‐Calle, V., Levenga, J., Gu, J., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0126-z · Cited by 63 · see citing works
Self-citationAntibody-DerivedIn VivoImaging of Tau Pathology
Krishnaswamy, S., Lin, Y., Rajamohamedsait, W. J., Rajamohamedsait, H. B., Krishnamurthy, P., & Sigurdsson, E. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2755-14.2014 · Cited by 62 · see citing works
Self-citationp-Tau immunotherapy reduces soluble and insoluble tau in aged 3xTg-AD mice
Walls, K. C., Ager, R. R., Vasilevko, V., Cheng, D., Medeiros, R., & LaFerla, F. M. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.05.047 · Cited by 58 · see citing works
Schroeder, S. K., Joly‐Amado, A., Gordon, M. N., & Morgan, D. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9637-6 · Cited by 49 · see citing works
Sigurdsson, E. M., Lorens, S. A., Hejna, M. J., Dong, X.-W., & Lee, J. M. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00169-8 · Cited by 49 · see citing works
Self-citationPassive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies
d’Abramo, C., Acker, C. M., Jimenez, H. T., & Davies, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135774 · Cited by 48 · see citing works
Selenica, M.-L. B., Davtyan, H., Housley, S. B., Blair, L. J., Gillies, A., Nordhues, B. A., Zhang, B., Liu, J., Gestwicki, J. E., Lee, D. C., et al. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0152-0 · Cited by 40 · see citing works
Tau immunization: a cautionary tale?
Mably, A. J., Kanmert, D., Donald, J. M. M., Liu, W., Caldarone, B. J., Lemere, C. A., O’Nuallain, B., Kosik, K. S., & Walsh, D. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.11.022 · Cited by 31 · see citing works
Ando, K., Kabova, A., Stygelbout, V., Leroy, K., Héraud, C., Frédérick, C., Suain, V., Yılmaz, Z., Authelet, M., Dedecker, R., et al. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132237 · Cited by 25 · see citing works
Harnessing the Immune System for Treatment and Detection of Tau Pathology
Congdon, E. E., Krishnaswamy, S., & Sigurdsson, E. M. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132435 · Cited by 20 · see citing works
Self-citationBoutajangout, A., Li, Y. S., Quartermain, D., & Sigurdsson, E. M. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-551-0_35 · Cited by 10 · see citing works
Self-citationTroquier, L., Caillierez, R., Burnouf, S., Kervoaze, G., Grosjean, M. E., Zommer, N., Sergeant, N., Lassalle, P., Blum, D. L., & Buée, L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.05.1402 · Cited by 4 · see citing works
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- [26]Castillo-Carranza DL Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds J. Alzheimers. Dis. 2014 40 Suppl 1 S97 S111 10.3233/JAD-132477 24603946 · DOI
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- Authors
- Rajamohamedsait, H., Rasool, S., Rajamohamedsait, W., Lin, Y., & Sigurdsson, E. M.
- Affiliations
- New York University (US)
- Corresponding author
- Sigurdsson, Einar M.
- Venue
- Scientific Reports
- Published
- 2017-12-06
- Volume
- 7
- Issue
- 1
- Pages
- 17034-17034
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5719023
- OpenAlex
- W2772204364
- Cited by
- 49
- References
- 58
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 7
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (NIH-R01, 1r24od018339-01, 1r24od018340-01, NS077239)
- National Institute on Aging (R01AG020197, R01AG032611)
- National Institute of Neurological Disorders and Stroke (R01NS077239)
- Topics
- Health Sciences › Medicine › Physiology › 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
- Alzheimer's disease, amyloid-beta, 3xTg-AD mice, prophylactic immunotherapy, tau pathology, amyloid-beta deposition, microglial activation, microhemorrhages, sex differences
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Female, Immunoglobulin G, Image Processing, Computer-Assisted, Immunotherapy, Male, Mice, Inbred C57BL, Mice, Transgenic, Vaccination, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, Mice, Presenilin-1, CA1 Region, Hippocampal
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