Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

Janus, Christopher; Pearson, Jacqueline; McLaurin, JoAnne; Mathews, Paul M.; Jiang, Ying; Schmidt, Stephen D.; Chishti, M. Azhar; Horne, Patrick; Heslin, Donna; French, Janet; Mount, Howard T.J.; Nixon, Ralph A.; Mercken, Marc; Bergeron, Catherine; Fraser, Paul E.; St George-Hyslop, Peter; Westaway, David

doi:10.1038/35050110

Cited by 1,431Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

Janus, Christopher, Pearson, Jacqueline, McLaurin, JoAnne, Mathews, Paul M., Jiang, Ying, Schmidt, Stephen D., Chishti, M. Azhar, Horne, Patrick +9 more·2000·Nature

DOI 10.1038/35050110

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Abstract

Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.

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The chosen experimental paradigms were successfully used in the lab to demonstrate impairment in APP CRND8 mice.
“The chosen experimental paradigms were successfully used in our lab to demonstrate impairment in APP CRND8 mice, and focused on spatial learning and reference memory evaluated in WM test [9,10,13] and conditioned taste aversion, a form of Pavlovian associative learning, [34], in addition to the context and tone conditioned fear memory paradigm [25]”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [13]

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Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · see citing works
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models
Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G.-Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R. C., Nicoll, R. A., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3228 · Cited by 1,123 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M., Lomakin, A., Benedek, G. B., Selkoe, D. J., & Teplow, D. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25945 · Cited by 1,046 · see citing works

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Uttara, B., Singh, A., Zamboni, P., & Mahajan, R. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602823 · Cited by 3,378 · see citing works
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Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
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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 · see citing works
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LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · see citing works
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H. Ferreira-Vieira, T., M. Guimaraes, I., R. Silva, F., & M. Ribeiro, F. (2016) · Current Neuropharmacology · doi:10.2174/1570159x13666150716165726 · Cited by 1,551 · see citing works
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Soto, C. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1007 · Cited by 1,506 · see citing works
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Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y.-S., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00317-8 · Cited by 1,447 · see citing works
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Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
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Orgogozo, J.-M., Gilman, S., Dartigues, J.-F., Laurent, B., Puel, M., Kirby, L. C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000073623.84147.a8 · Cited by 1,356 · see citing works
Intraneuronal Aβ Causes the Onset of Early Alzheimer’s Disease-Related Cognitive Deficits in Transgenic Mice
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
Curcumin has potent anti‐amyloidogenic effects for Alzheimer's β‐amyloid fibrils in vitro
Ono, K., Hasegawa, K., Naiki, H., & Yamada, M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20025 · Cited by 1,254 · see citing works
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Wyss-Coray, T., & Mucke, L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00794-8 · Cited by 1,235 · see citing works
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207 · see citing works
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease
Bezprozvanny, I., & Mattson, M. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.005 · Cited by 938 · see citing works
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Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
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The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal
Hardy, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06181.x · Cited by 814 · see citing works
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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
The case for rejecting the amyloid cascade hypothesis
Herrup, K. (2015) · Nature Neuroscience · doi:10.1038/nn.4017 · Cited by 768 · see citing works
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models
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
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Background
Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques
Lee, J.-H., Yang, D.-S., Goulbourne, C. N., Im, E., Stavrides, P., Pensalfini, A., Chan, H., Bouchet-Marquis, C., Bleiwas, C., Berg, M. J., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01084-8 · Cited by 638 · see citing works
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Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626 · see citing works
Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
D'Amelio, M., Cavallucci, V., Middei, S., Marchetti, C., Pacioni, S., Ferri, A., Diamantini, A., De Zio, D., Carrara, P., Battistini, L., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2709 · Cited by 572 · see citing works
γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in?
Sisodia, S. S., & St George-Hyslop, P. H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn785 · Cited by 512 · see citing works
Self-citation
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McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · see citing works
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Wyss-Coray, T., Yan, F., Lin, A. H.-T., Lambris, J. D., Alexander, J. J., Quigg, R. J., & Masliah, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162350199 · Cited by 446 · see citing works
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Bohrmann, B., Baumann, K., Benz, J., Gerber, F., Huber, W., Knoflach, F., Messer, J., Oroszlan, K., Rauchenberger, R., Richter, W. F., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110977 · Cited by 448 · see citing works
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Schenk, D. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn938 · Cited by 436 · see citing works
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Yang, D.-S., Stavrides, P., Mohan, P. S., Kaushik, S., Kumar, A., Ohno, M., Schmidt, S. D., Wesson, D., Bandyopadhyay, U., Jiang, Y., et al. (2011) · Brain · doi:10.1093/brain/awq341 · Cited by 429 · see citing works
Self-citation
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De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., Bigio, E. H., Jerecic, J., Acton, P. J., Shughrue, P. J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.029 · Cited by 432 · see citing works
Reversible memory loss in a mouse transgenic model of Alzheimer’s disease
Kotilinek, L. A., Bacskai, B., Westerman, M., Kawarabayashi, T., Younkin, L., Hyman, B. T., Younkin, S., & Ashe, K. H. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06331.2002 · Cited by 420 · see citing works
Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer's disease-like neuropathology
Bard, F., Barbour, R., Cannon, C., Carretto, R., Fox, M., Games, D., Guido, T., Hoenow, K., Hu, K., Johnson-Wood, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436286100 · Cited by 411 · see citing works
Aβ is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis
Herzig, M. C., Winkler, D. T., Burgermeister, P., Pfeifer, M., Kohler, E., Schmidt, S. D., Danner, S., Abramowski, D., Stürchler-Pierrat, C., Bürki, K., et al. (2004) · Nature Neuroscience · doi:10.1038/nn1302 · Cited by 391 · see citing works
Self-citation
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Microglia and inflammatory mechanisms in the clearance of amyloid β peptide
Rogers, J., Strohmeyer, R., Kovelowski, C. J., & Li, R. (2002) · Glia · doi:10.1002/glia.10153 · Cited by 381 · see citing works
A -related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy
Scolding, N. J. (2005) · Brain · doi:10.1093/brain/awh379 · Cited by 372 · see citing works
The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease
the Synaptic Health Endpoints Working Group, Colom-Cadena, M., Spires-Jones, T., Zetterberg, H., Blennow, K., Caggiano, A., DeKosky, S. T., Fillit, H., Harrison, J. E., Schneider, L. S., et al. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00588-4 · Cited by 328 · see citing works
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Bayer, A. J., Bullock, R., Jones, R. W., Wilkinson, D., Paterson, K. R., Jenkins, L., Millais, S. B., & Donoghue, S. (2005) · Neurology · doi:10.1212/01.wnl.0000148604.77591.67 · Cited by 356 · see citing works
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Lambert, M. P., Viola, K. L., Chromy, B. A., Chang, L., Morgan, T. E., Yu, J., Venton, D. L., Krafft, G. A., Finch, C. E., & Klein, W. L. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00592.x · Cited by 349 · see citing works
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Doens, D., & Fernández, P. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-48 · Cited by 348 · see citing works
Transgenic mouse models of Alzheimer’s disease.
Elder, G. A., Gama Sosa, M. A., & De Gasperi, R. (2010) · Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20159 · Cited by 336 · see citing works
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Weiner, H. L., & Frenkel, D. (2006) · Nature Reviews Immunology · doi:10.1038/nri1843 · Cited by 335 · see citing works
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Wisniewski, T., & Goñi, F. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.064 · Cited by 284 · see citing works
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Burgess, A., Dubey, S., Yeung, S., Hough, O., Eterman, N., Aubert, I., & Hynynen, K. (2014) · Radiology · doi:10.1148/radiol.14140245 · Cited by 286 · see citing works
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Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000042478.08543.f7 · Cited by 282 · see citing works
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Brody, D. L., & Holtzman, D. M. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125529 · Cited by 250 · see citing works
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Liu, Q., Xi, Y., Wang, Q., Liu, J., Li, P., Meng, X., Liu, K., Chen, W., Liu, X., & Liu, Z. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.04.005 · Cited by 241 · see citing works
Microglial chemotaxis, activation, and phagocytosis of amyloid β-peptide as linked phenomena in Alzheimer's disease
Rogers, J., & Lue, L.-F. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(01)00040-7 · Cited by 236 · see citing works
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Lemere, C. A., Beierschmitt, A., Iglesias, M., Spooner, E. T., Bloom, J. K., Leverone, J. F., Zheng, J. B., Seabrook, T. J., Louard, D., Li, D., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63296-8 · Cited by 230 · see citing works
Immunotherapy for Alzheimer’s disease: Key Symposium: Immunotherapy for Alzheimer’s disease
Morgan, D. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02315.x · Cited by 225 · see citing works
Neurotherapeutic applications of nanoparticles in Alzheimer’s disease
Sahni, J. K., Doggui, S., Ali, J., Baboota, S., Dao, L., & Ramassamy, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.033 · Cited by 219 · see citing works
Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease
Farfara, D., Lifshitz, V., & Frenkel, D. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00314.x · Cited by 216 · see citing works
Mouse Models of Alzheimer’s Disease
Yokoyama, M., Kobayashi, H., Tatsumi, L., & Tomita, T. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.912995 · Cited by 213 · see citing works
Familial Amyloid Polyneuropathy: Receptor for Advanced Glycation End Products-Dependent Triggering of Neuronal Inflammatory and Apoptotic Pathways
Sousa, M. M., Du Yan, S., Fernandes, R., Guimarães, A., Stern, D., & Saraiva, M. J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07576.2001 · Cited by 212 · see citing works
Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration
Wilcock, D. M., Munireddy, S. K., Rosenthal, A., Ugen, K. E., Gordon, M. N., & Morgan, D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.09.015 · Cited by 202 · see citing works
Antibody Uptake into Neurons Occurs Primarily via Clathrin-dependent Fcγ Receptor Endocytosis and Is a Prerequisite for Acute Tau Protein Clearance
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
Ageing of the brain
Anderton, B. H. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00426-2 · Cited by 187 · see citing works
T-Cells in Alzheimer's Disease
Town, T., Tan, J., Flavell, R. A., & Mullan, M. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:3:255 · Cited by 183 · see citing works
Galantamine-induced Amyloid-β Clearance Mediated via Stimulation of Microglial Nicotinic Acetylcholine Receptors
Takata, K., Kitamura, Y., Saeki, M., Terada, M., Kagitani, S., Kitamura, R., Fujikawa, Y., Maelicke, A., Tomimoto, H., Taniguchi, T., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142356 · Cited by 176 · see citing works
Amyloid β-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin
Malito, E., Hulse, R. E., & Tang, W.-J. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8112-4 · Cited by 176 · see citing works
A Single Ascending Dose Study of Bapineuzumab in Patients With Alzheimer Disease
Black, R. S., Sperling, R. A., Safirstein, B., Motter, R. N., Pallay, A., Nichols, A., & Grundman, M. (2010) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3181c53b00 · Cited by 170 · see citing works
Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology
Serrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., et al. (2010) · Brain · doi:10.1093/brain/awq056 · Cited by 159 · see citing works
Conditional Inactivation of Presenilin 1 Prevents Amyloid Accumulation and Temporarily Rescues Contextual and Spatial Working Memory Impairments in Amyloid Precursor Protein Transgenic Mice
Saura, C. A., Chen, G., Malkani, S., Choi, S.-Y., Takahashi, R. H., Zhang, D., Gouras, G. K., Kirkwood, A., Morris, R. G. M., & Shen, J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1247-05.2005 · Cited by 157 · see citing works
Amyloid-β immunisation for Alzheimer's disease
Wisniewski, T., & Konietzko, U. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70170-4 · Cited by 155 · see citing works
Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade
Honjo, K., Black, S. E., & Verhoeff, N. P. L. G. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100015547 · Cited by 152 · see citing works
Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha
Kuboyama, T., Tohda, C., Zhao, J., Nakamura, N., Hattori, M., & Komatsu, K. (2002) · Neuroreport · doi:10.1097/00001756-200210070-00005 · Cited by 146 · see citing works
Alzheimer's disease amyloid β-protein and synaptic function
Ondrejcak, T., Klyubin, I., Hu, N.-W., Barry, A. E., Cullen, W. K., & Rowan, M. J. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8091-0 · Cited by 146 · see citing works
Biochemistry and Molecular Biology of Amyloid β‐Protein and the Mechanism of Alzheimer's Disease
(2008) · Handbook of Clinical Neurology · doi:10.1016/s0072-9752(07)01223-7 · Cited by 137 · see citing works
Neuropathology after active Aβ42 immunotherapy: implications for Alzheimer’s disease pathogenesis
Boche, D., Denham, N., Holmes, C., & Nicoll, J. A. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0719-5 · Cited by 135 · see citing works
Parenchymal and vascular Aβ‐deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease
Thal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134 · see citing works
Immunotherapy Reduces Vascular Amyloid- in PDAPP Mice
Schroeter, S., Khan, K., Barbour, R., Doan, M., Chen, M., Guido, T., Gill, D., Basi, G., Schenk, D., Seubert, P., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2377-07.2008 · Cited by 133 · see citing works
Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides
Hinrich, A. J., Jodelka, F. M., Chang, J. L., Brutman, D., Bruno, A. M., Briggs, C. A., James, B. D., Stutzmann, G. E., Bennett, D. A., Miller, S. A., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201505846 · Cited by 127 · see citing works
ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing
Satoh, K., Abe-Dohmae, S., Yokoyama, S., St George-Hyslop, P., & Fraser, P. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.655076 · Cited by 128 · see citing works
Self-citation
Mitochondria in Alzheimer's disease
Swerdlow, R. H., & Kish, S. J. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)53013-0 · Cited by 126 · see citing works
Internalized Antibodies to the Aβ Domain of APP Reduce Neuronal Aβ and Protect against Synaptic Alterations
Tampellini, D., Magrané, J., Takahashi, R. H., Li, F., Lin, M. T., Almeida, C. G., & Gouras, G. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700373200 · Cited by 118 · see citing works
Immunotherapy Targeting Pathological Tau Protein in Alzheimer's Disease and Related Tauopathies
Sigurdsson, E. M. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-15202 · Cited by 116 · see citing works
Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease
Ambrée, O., Richter, H., Sachser, N., Lewejohann, L., Dere, E., de Souza Silva, M. A., Herring, A., Keyvani, K., Paulus, W., & Schäbitz, W.-R. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.010 · Cited by 115 · see citing works
Insights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models
Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-6463fje · Cited by 113 · see citing works
Immunogenicity, Efficacy, Safety, and Mechanism of Action of Epitope Vaccine (Lu AF20513) for Alzheimer's Disease: Prelude to a Clinical Trial
Davtyan, H., Ghochikyan, A., Petrushina, I., Hovakimyan, A., Davtyan, A., Poghosyan, A., Marleau, A. M., Movsesyan, N., Kiyatkin, A., Rasool, S., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4672-12.2013 · Cited by 112 · see citing works
Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease
Dickstein, D. L., Biron, K. E., Ujiie, M., Pfeifer, C. G., Jeffries, A. R., & Jefferies, W. A. (2006) · The FASEB Journal · doi:10.1096/fj.05-3956com · Cited by 111 · see citing works
BACE1 gene deletion: Impact on behavioral function in a model of Alzheimer’s disease
Kobayashi, D., Zeller, M., Cole, T., Buttini, M., McConlogue, L., Sinha, S., Freedman, S., Morris, R. G. M., & Chen, K. S. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.01.002 · Cited by 111 · see citing works
Role of the Immune System in the Pathogenesis, Prevention and Treatment of Alzheimer??s Disease
Blasko, I., & Grubeck-Loebenstein, B. (2003) · Drugs & Aging · doi:10.2165/00002512-200320020-00002 · Cited by 108 · see citing works
Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease
Watts, J. C., Giles, K., Grillo, S. K., Lemus, A., DeArmond, S. J., & Prusiner, S. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019034108 · Cited by 109 · see citing works
Site-specific UBITh® amyloid-β vaccine for immunotherapy of Alzheimer's disease
Wang, C. Y., Finstad, C. L., Walfield, A. M., Sia, C., Sokoll, K. K., Chang, T.-Y., Fang, X. D., Hung, C. H., Hutter-Paier, B., & Windisch, M. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.01.031 · Cited by 98 · see citing works
Activity changes and marked stereotypic behavior precede Aβ pathology in TgCRND8 Alzheimer mice
Ambrée, O., Touma, C., Görtz, N., Keyvani, K., Paulus, W., Palme, R., & Sachser, N. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.009 · Cited by 93 · see citing works
Microglia in Alzheimer's Disease: It's All About Context
Weitz, T. M., & Town, T. (2012) · International Journal of Alzheimer's Disease · doi:10.1155/2012/314185 · Cited by 95 · see citing works
Amyloid β: one of three danger‐associated molecules that are secondary inducers of the proinflammatory cytokines that mediate <scp>A</scp>lzheimer's disease
Clark, I. A., & Vissel, B. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13181 · Cited by 84 · see citing works
Normal cognition in transgenic BRI2-Aβ mice
Kim, J., Chakrabarty, P., Hanna, A., March, A., Dickson, D. W., Borchelt, D. R., Golde, T., & Janus, C. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-15 · Cited by 83 · see citing works
Self-citation
Drugs targeting alzheimer’s disease: Some things old and some things new
Michaelis, M. L. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.035840 · Cited by 78 · see citing works
Aβ immunotherapy for Alzheimer’s disease: effects on apoE and cerebral vasculopathy
Sakai, K., Boche, D., Carare, R., Johnston, D., Holmes, C., Love, S., & Nicoll, J. A. R. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1340-9 · Cited by 72 · see citing works
Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer’s Disease
Vyas, Y., Montgomery, J. M., & Cheyne, J. E. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00266 · Cited by 66 · see citing works
Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of down Syndrome.
Goodliffe, J. W., Olmos-Serrano, J. L., Aziz, N. M., Pennings, J. L. A., Guedj, F., Bianchi, D. W., & Haydar, T. F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2513-15.2016 · Cited by 65 · see citing works
Central and peripheral circadian clocks and their role in Alzheimer's disease
Chauhan, R., Chen, K.-F., Kent, B. A., & Crowther, D. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.030627 · Cited by 58 · see citing works
How plausible is an Alzheimer’s disease vaccine?
Cacabelos, R. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1667329 · Cited by 54 · see citing works
Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer's disease
Alexander, G., Hanna, A., Serna, V., Younkin, L., Younkin, S., & Janus, C. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.07.016 · Cited by 51 · see citing works
Self-citation
Prospects for strain-specific immunotherapy in Alzheimer’s disease and tauopathies
Bittar, A., Sengupta, U., & Kayed, R. (2018) · npj Vaccines · doi:10.1038/s41541-018-0046-8 · Cited by 50 · see citing works

Authors: Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., Mount, H. T. J., Nixon, R. A., Mercken, M., Bergeron, C., Fraser, P. E., St George-Hyslop, P., & Westaway, D.
Affiliations: University of Toronto (CA)
New York University (US)
Janssen (Belgium) (BE)
University Health Network (CA)
ORCID: Janus, Christopher
McLaurin, JoAnne
Mathews, Paul M.
Mount, Howard T.J.
Nixon, Ralph A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2000-12
Volume: 408
Issue: 6815
Pages: 979-982
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35050110
OpenAlex: W1965275873
Cited by: 1,431
References: 5
Citations by year: 2026: 7 · 2025: 11 · 2024: 16 · 2023: 22 · 2022: 21 · 2021: 15 · 2020: 26 · 2019: 26 · 2018: 25 · 2017: 31 · 2016: 30 · 2015: 35 · 2014: 46 · 2013: 59 · 2012: 61
FWCI: 69.52
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Medical Research Council
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: amyloid-beta immunization, Alzheimer's disease, amyloid plaques, cognitive impairment, TgCRND8 mice, amyloid hypothesis, amyloid-beta processing, amyloid precursor protein
MeSH terms: Alzheimer Disease, Amyloid, Animals, Disease Models, Animal, Cricetinae, Hippocampus, Humans, Mesocricetus, Mice, Inbred C3H, Mice, Transgenic, Peptide Fragments, Vaccination, Amyloid beta-Peptides, Maze Learning, Mice, Plaque, Amyloid, Islet Amyloid Polypeptide

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Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease

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