Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β
Open accessAbstract
The amyloid-β lowering capacity of anti-Aβ antibodies has been demonstrated in transgenic models of Alzheimer's disease (AD) and in AD patients. While the mechanism of immunotherapeutic amyloid-β removal is controversial, antibody-mediated sequestration of peripheral Aβ versus microglial phagocytic activity and disassembly of cerebral amyloid (or a combination thereof) has been proposed. For successful Aβ immunotherapy, we hypothesized that high affinity antibody binding to amyloid-β plaques and recruitment of brain effector cells is required for most efficient amyloid clearance. Here we report the generation of a novel fully human anti-Aβ antibody, gantenerumab, optimized in vitro for binding with sub-nanomolar affinity to a conformational epitope expressed on amyloid-β fibrils using HuCAL(®) phage display technologies. In peptide maps, both N-terminal and central portions of Aβ were recognized by gantenerumab. Remarkably, a novel orientation of N-terminal Aβ bound to the complementarity determining regions was identified by x-ray analysis of a gantenerumab Fab-Aβ(1-11) complex. In functional assays gantenerumab induced cellular phagocytosis of human amyloid-β deposits in AD brain slices when co-cultured with primary human macrophages and neutralized oligomeric Aβ42-mediated inhibitory effects on long-term potentiation in rat brain. In APP751(swedish)xPS2(N141I) transgenic mice, gantenerumab showed sustained binding to cerebral amyloid-β and, upon chronic treatment, significantly reduced small amyloid-β plaques by recruiting microglia and prevented new plaque formation. Unlike other Aβ antibodies, gantenerumab did not alter plasma Aβ suggesting undisturbed systemic clearance of soluble Aβ. These studies demonstrated that gantenerumab preferentially interacts with aggregated Aβ in the brain and lowers amyloid-β by eliciting effector cell-mediated clearance.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 decrease in amyloid of about 5 centiloids from baseline with 1.0 mg/kg bapineuzumab was very modest and therapeutically irrelevant.
“The decrease in amyloid (~5 CL) from baseline in the 1.0 mg/kg group was very modest and therapeutically irrelevant.”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [61]
Bapineuzumab caused significant ARIA-E but removed very little amyloid.
“For example, bapinezumab caused significant ARIA-E but removed very little amyloid 61 .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [61]
Bapineuzumab has an incidence of ARIA-E of 9%.
“| Bapineuzumab | 0.3 | ~7 a /12 | 0 | 71 | 0 | 9 | - |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [61]
Bapineuzumab has a normalized rate of amyloid removal of 0 CL/4 wk/10mg/kg.
“| Bapineuzumab | 0.3 | ~7 a /12 | 0 | 71 | 0 | 9 | - |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [61]
Bapineuzumab removes approximately 7 centiloids in 12 patients.
“| Bapineuzumab | 0.3 | ~7 a /12 | 0 | 71 | 0 | 9 | - |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,299 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1× · see citing works
“Cryosections of mouse brains and postmortem human frontal cortices from AD cases at Braak stage VI [29] were prepared at 10 and 20 m nominal thickness, treated with ice-cold acetone and washed in PBS.”
MethodThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
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
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
3D structure of Alzheimer's amyloid-β(1–42) fibrils
Lührs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Döbeli, H., Schubert, D. A., & Riek, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506723102 · Cited by 2,001 · see citing works
Self-citationAβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., et al. (2000) · Nature · doi:10.1038/35050110 · Cited by 1,431 · see citing works
Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61075-2 · Cited by 1,416 · see citing works
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
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
Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization
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
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000159740.16984.3c · Cited by 1,329 · see citing works
DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298 · see citing works
In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis
Stine, W. B., Dahlgren, K. N., Krafft, G. A., & LaDu, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210207200 · Cited by 1,015 · see citing works
Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab
Ostrowitzki, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.1538 · Cited by 431 · cited 2× · see citing works
“with primary human microglia cells [32] further”
MethodDisaggregation of Alzheimer β-amyloid by site-directed mAb
Solomon, B., Koppel, R., Frankel, D., & Hanan, E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4109 · Cited by 420 · see citing works
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
Gessner, J. E., Heiken, H., Tamm, A., & Schmidt, R. E. (1998) · Annals of Hematology · doi:10.1007/s002770050396 · Cited by 410 · see citing works
Macromolecular permeability across the blood-nerve and blood-brain barriers.
Poduslo, J. F., Curran, G. L., & Berg, C. T. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5705 · Cited by 377 · see citing works
Yang, W.-P., Green, K., Pinz-Sweeney, S., Briones, A. T., Burton, D. R., & Barbas, C. F. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0626 · Cited by 333 · see citing works
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-β<i>In Vivo</i>by Immunotherapy
Bacskai, B. J., Kajdasz, S. T., McLellan, M. E., Games, D., Seubert, P., Schenk, D., & Hyman, B. T. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07873.2002 · Cited by 323 · see citing works
Klyubin, I., Betts, V., Welzel, A. T., Blennow, K., Zetterberg, H., Wallin, A., Lemere, C. A., Cullen, W. K., Peng, Y., Wisniewski, T., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5161-07.2008 · Cited by 321 · see citing works
Racke, M. M., Boone, L. I., Hepburn, D. L., Parsadainian, M., Bryan, M. T., Ness, D. K., Piroozi, K. S., Jordan, W. H., Brown, D. D., Hoffman, W. P., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4337-04.2005 · Cited by 320 · see citing works
Consequence of Aβ immunization on the vasculature of human Alzheimer's disease brain
Boche, D., Zotova, E., Weller, R. O., Love, S., Neal, J. W., Pickering, R. M., Wilkinson, D., Holmes, C., & Nicoll, J. A. R. (2008) · Brain · doi:10.1093/brain/awn261 · Cited by 316 · see citing works
Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide.
Solomon, B., Koppel, R., Hanan, E., & Katzav-Gozansky, T. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.452 · Cited by 314 · see citing works
Broadwell, R. D., & Sofroniew, M. V. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1059 · Cited by 310 · see citing works
Induction of tolerance by monoclonal antibody therapy
Benjamin, R. J., & Waldmann, H. (1986) · Nature · doi:10.1038/320449a0 · Cited by 299 · see citing works
Weller, R. O., Boche, D., & Nicoll, J. A. R. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0498-z · Cited by 297 · see citing works
Vellas, B. J., Black, R. S., Thal, L. J., Fox, N. C., Daniels, M., McLennan, G., Tompkins, C., Leibman, C. W., Pomfret, M., & Grundman, M. (2009) · Current Alzheimer Research · doi:10.2174/156720509787602852 · Cited by 256 · see citing works
Human immunoglobulin allotypes
Jefferis, R., & Lefranc, M. (2009) · mAbs · doi:10.4161/mabs.1.4.9122 · Cited by 237 · see citing works
Deane, R., Sagare, A. P., Hamm, K., Parisi, M., LaRue, B., Guo, H., Wu, Z., Holtzman, D. M., & Zloković, B. V. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3697-05.2005 · Cited by 233 · see citing works
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
Amyloid-β Immunization Effectively Reduces Amyloid Deposition in FcRγ-/-Knock-Out Mice
Das, P., HOWARD, V. G., Loosbrock, N., Dickson, D. W., Murphy, M. P., & Golde, T. E. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-24-08532.2003 · Cited by 212 · see citing works
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
Britschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., Rajadas, J., Zhang, H., Tomooka, B., Robinson, W. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904866106 · Cited by 201 · see citing works
Richards, J., Higgins, G., Ouagazzal, A., Ozmen, L., Kew, J., Bohrmann, B., Malherbe, P., Brockhaus, M., Loetscher, H., Czech, C., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-26-08989.2003 · Cited by 197 · see citing works
Self-citationBussière, T., Bard, F., Barbour, R., Grajeda, H., Guido, T., Khan, K., Schenk, D., Games, D., Seubert, P. A., & Buttini, M. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63360-3 · Cited by 169 · see citing works
Wilcock, D. M., Alamed, J., Gottschall, P. E., Grimm, J., Rosenthal, A., Pons, J., Ronan, V., Symmonds, K., Gordon, M. N., & Morgan, D. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0695-06.2006 · Cited by 154 · see citing works
Koenigsknecht-Talboo, J., Meyer-Luehmann, M., Parsadanian, M., Garcia-Alloza, M., Finn, M. B., Hyman, B. T., Bacskai, B. J., & Holtzman, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4147-08.2008 · Cited by 149 · see citing works
Du, Y. (2003) · Brain · doi:10.1093/brain/awg191 · Cited by 136 · see citing works
Rauchenberger, R., Borges, E., Thomassen-Wolf, E., Rom, E., Adar, R., Yaniv, Y., Malka, M., Chumakov, I., Kotzer, S., Resnitzky, D., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303164200 · Cited by 127 · see citing works
Self-citationPhagocytosis of Amyloid-β and Inflammation: Two Faces of Innate Immunity in Alzheimer's Disease
Fiala, M., Cribbs, D. H., Rosenthal, M. J., & Bernard, G. W. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11406 · Cited by 124 · see citing works
Wang, A., Das, P., Switzer, R. C., Golde, T. E., & Jankowsky, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5077-10.2011 · Cited by 118 · 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
Investigation of the Influence of FcRn on the Distribution of IgG to the Brain
Garg, A., & Balthasar, J. P. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9129-9 · Cited by 108 · see citing works
Boche, D., & Nicoll, J. A. R. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00134.x · Cited by 104 · see citing works
Banks, W. A., Farr, S. A., Morley, J. E., Wolf, K. M., Geylis, V., & Steinitz, M. O. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.05.005 · Cited by 103 · see citing works
In vitro affinity maturation of human GM-CSF antibodies by targeted CDR-diversification
Steidl, S., Ratsch, O., Brocks, B., Dürr, M. C., & Thomassen-Wolf, E. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.07.013 · Cited by 94 · see citing works
Antibody Capture of Soluble Aβ Does Not Reduce Cortical Aβ Amyloidosis in the PDAPP Mouse
Seubert, P. A., Barbour, R., Khan, K., Motter, R. N., Tang, P., Kholodenko, D., Kling, K., Schenk, D., Johnson‐Wood, K., Schroeter, S., et al. (2008) · Neurodegenerative Diseases · doi:10.1159/000112834 · Cited by 66 · see citing works
Miles, L. A., Wun, K. S., Crespi, G. A. N., Fodero‐Tavoletti, M. T., Galatis, D., Bagley, C. J., Beyreuther, K. T., Masters, C. L., Cappai, R., McKinstry, W. J., et al. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.12.036 · Cited by 52 · see citing works
Quantitative and Mechanistic Studies of A&#946; Immunotherapy
Golde, T., Das, P., & Levites, Y. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787601830 · Cited by 46 · cited 2× · see citing works
“The similarity in the pharmacokinetic profiles of investigated anti-A antibodies and A indicates a stabilization of soluble A by binding to the circulating anti-A antibodies [35, 53].”
BackgroundBasi, G. S., Feinberg, H., Oshidari, F., Anderson, J., Barbour, R., Baker, J., Comery, T. A., Diep, L., Gill, D. S., Johnson‐Wood, K., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.045187 · Cited by 45 · see citing works
Waldmann, H., Adams, E., & Cobbold, S. P. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00632.x · Cited by 38 · see citing works
Narlawar, R., Pérez‐Revuelta, B. I., Haass, C., Steiner, H., Schmidt, B., & Baumann, K. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0610200 · Cited by 36 · see citing works
Self-citationThermodynamic Studies on the Interaction of Antibodies with β-Amyloid Peptide
Brockhaus, M., Ganz, P., Huber, W., Bohrmann, B., Loetscher, H., & Seelig, J. (2007) · The Journal of Physical Chemistry B · doi:10.1021/jp0664059 · Cited by 24 · see citing works
Self-citationStructures of Aβ-Related Peptide−Monoclonal Antibody Complexes,
Gardberg, A. S., Dice, L. T., Pridgen, K., Ko, J., Patterson, P. H., Ou, S. K.-H., Wetzel, R. B., & Dealwis, C. G. (2009) · Biochemistry · doi:10.1021/bi9001216 · Cited by 16 · see citing works
Winkler, D. T., Abramowski, D., Danner, S., Zurini, M. G. M., Paganetti, P., Tolnay, M., & Staufenbiel, M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.030 · Cited by 14 · see citing works
Development and Characterization of a TAPIR-Like Mouse Monoclonal Antibody to Amyloid-β
Wang, J., Hara, H., Makifuchi, T., & Tabira, T. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14204 · Cited by 12 · see citing works
Basi, G. S., Feinberg, H., Oshidari, F., Anderson, J. J., Barbour, R., Baker, J. E., Comery, T. A., Diep, L., Gill, D. R., Johnson‐Wood, K., et al. (2012) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) · Cited by 12 · see citing works
Macromolecular permeability across the blood nerve and blood brain barriers
Poduslo, J. F. (1994) · Neurobiology of Aging · doi:10.1016/0197-4580(94)92593-3 · Cited by 9 · see citing works
Anti-amyloid antibody drugs in clinical testing for Alzheimer's disease.
Bednar, M. M. (2009) · PubMed · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
Therapeutics of Alzheimer's disease: Past, present and future
Anand, R., Gill, K. D., & Mahdi, A. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.004 · Cited by 748 · see citing works
“Gantenerumab preferentially interacts with aggregated Ab in the brain without affecting plasma Ab levels suggesting its systemic specificity (Bohrmann et al., 2012); the effect is dose dependent (Ostrowitzki et al., 2012).”
BackgroundClinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · see citing works
Nguyen, P. H., Ramamoorthy, A., Sahoo, B. R., Zheng, J., Faller, P., Straub, J. E., Domı́nguez, L., Shea, J., Dokholyan, N. V., Simone, A. D., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01122 · Cited by 676 · see citing works
Niewoehner, J., Bohrmann, B., Collin, L., Urich, E., Sade, H., Maier, P., Rueger, P., Stracke, J. O., Lau, W., Tissot, A. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.061 · Cited by 622 · see citing works
Self-citationAnti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise
van Dyck, C. H. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.010 · Cited by 568 · see citing works
Amyloid-Beta: A Crucial Factor in Alzheimer's Disease
Sadigh‐Eteghad, S., Sabermarouf, B., Majdi, A., Talebi, M., Farhoudi, M., & Mahmoudi, J. (2014) · Medical Principles and Practice · doi:10.1159/000369101 · Cited by 542 · see citing works
Update on Alzheimer’s Disease Therapy and Prevention Strategies
Graham, W. V., Bonito-Oliva, A., & Sakmar, T. P. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-042915-103753 · Cited by 506 · see citing works
CSF, blood-brain barrier, and brain drug delivery
Pardridge, W. M. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1171315 · Cited by 508 · see citing works
A Plaque-Specific Antibody Clears Existing β-amyloid Plaques in Alzheimer's Disease Mice
DeMattos, R. B., Lu, J., Tang, Y., Racke, M. M., DeLong, C. A., Tzaferis, J. A., Hole, J. T., Forster, B. M., McDonnell, P. C., Liu, F., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.029 · Cited by 442 · see citing works
Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab
Ostrowitzki, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.1538 · Cited by 431 · see citing works
Söderberg, L., Johannesson, M., Nygren, P., Laudon, H., Eriksson, F., Osswald, G., Möller, C., & Lannfelt, L. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01308-6 · Cited by 444 · see citing works
Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier
Lajoie, J. M., & Shusta, E. V. (2015) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124852 · Cited by 399 · see citing works
Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain
Pardridge, W. M. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00373 · Cited by 405 · see citing works
The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind
Ricciarelli, R., & Fedele, E. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170116143743 · Cited by 380 · see citing works
“Gantenerumab is a human antibody directed against the aggregated forms of Aβ, which recognizes both the Nterminus and the mid-domain of Aβ [84, 85].”
BackgroundAnti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer’s Disease
Cummings, J. L., Osse, A. M. L., Cammann, D., Powell, J., & Chen, J. (2023) · BioDrugs · doi:10.1007/s40259-023-00633-2 · Cited by 396 · see citing works
“When APP751(Swedish) xPS2(N141I) transgenic mice received chronic treatment, gantenerumab reduced Aβ plaques via cell-mediated clearance and prevented new plaque formation [50].”
Tau Aggregation and Its Interplay with Amyloid-β
Nisbet, R. M., Polanco, J.-C., Ittner, L. M., & Götz, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-014-1371-2 · Cited by 359 · see citing works
“Clinical trials are currently being conducted for the next phase of immunotherapies, which have moved away from linear Aβ epitopes targeting soluble Aβ to those that recognize conformational epitopes on Aβ aggregates; for example SAR228810, Gantenerumab [11], BAN2401, Aducanumab, ACI-24 [64] and Crenezumab [1] (http:/…”
BackgroundStructural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β
Arndt, J. W., Qian, F., Smith, B. A., Quan, C., Kilambi, K. P., Bush, M. W., Walz, T., Pepinsky, R. B., Bussière, T., Hamann, S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-24501-0 · Cited by 364 · see citing works
Tolar, M., Abushakra, S., Hey, J. A., Porsteinsson, A., & Sabbagh, M. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00663-w · Cited by 354 · see citing works
Two phase 3 trials of gantenerumab in early Alzheimer's disease
Bateman, R. J., Smith, J., Donohue, M. C., Delmar, P., Abbas, R., Salloway, S., Wojtowicz, J., Blennow, K., Bittner, T., Black, S. E., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304430 · Cited by 314 · see citing works
BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease
Moussa‐Pacha, N. M., Abdin, S. M., Omar, H. A., Alniss, H. Y., & Al‐Tel, T. H. (2019) · Medicinal Research Reviews · doi:10.1002/med.21622 · Cited by 308 · see citing works
Immunotherapeutic Approaches for Alzheimer’s Disease
Wisniewski, T., & Goñi, F. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.064 · Cited by 284 · see citing works
Phage Display Derived Monoclonal Antibodies: From Bench to Bedside
Alfaleh, M. A., Alsaab, H. O., Mahmoud, A. B., Alkayyal, A. A., Jones, M. L., Mahler, S. M., & Hashem, A. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01986 · Cited by 280 · see citing works
Govindpani, K., McNamara, L. G., Smith, N. R., Vinnakota, C., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8050651 · Cited by 271 · see citing works
“Another two anti-Aβ mABs are currently in clinical trials—BAN2401, selective for Aβ protofibrils [447,448] and gantenerumab, selective for a specific folded conformation of aggregated Aβ [449].”
BackgroundShi, M., Chu, F., Zhu, F., & Zhu, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.870517 · Cited by 275 · see citing works
Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment
Folch, J., Petrov, D., Ettcheto, M., Abad, S., Sánchez-López, E., García, M. L., Olloquequi, J., Beas-Zarate, C., Auladell, C., & Camins, A. (2016) · Neural Plasticity · doi:10.1155/2016/8501693 · Cited by 270 · see citing works
“An advantage of this strategy compared to active immunization is that the proinflammatory T cellmediated immune reactions should not occur.”
BackgroundImmunotherapy for Alzheimer’s disease: targeting β-amyloid and beyond
Song, C., Shi, J., Zhang, P., Zhang, Y., Xu, J., Zhao, L., Zhang, R., Wang, H., & Chen, H. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00292-3 · Cited by 266 · see citing works
“Gantenerumab Gantenerumab (RO4909832) is a human IgG1 monoclonal antibody that binds to aggregated Aβ with high affinity and facilitates Aβ clearance via Fc receptor-mediated phagocytosis [51, 52].”
BackgroundNeurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches
Hussain, R., Zubair, H., Sarah, P., & Shahab, M. (2018) · Brain Sciences · doi:10.3390/brainsci8090177 · Cited by 233 · see citing works
“It binds both N-terminal and central amino acids of Aβ Phase III 225 mg SC [388]”
BackgroundKlein, G., Delmar, P., Voyle, N., Rehal, S., Hofmann, C., Abi-Saab, D., Andjelkovic, M., Ristic, S., Wang, G., Bateman, R., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0559-z · Cited by 212 · see citing works
A Historical Review of Brain Drug Delivery
Pardridge, W. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061283 · Cited by 219 · see citing works
Mullane, K., & Williams, M. J. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.11.014 · Cited by 212 · 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
“Gantenerumab bound to cerebral Aβ and enhanced the removal of small Aβ plaques by recruiting microglia, and prevented new plaque formation in PS2APP mice (Bohrmann et al., 2012).”
BackgroundKinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies
Linse, S. S., Scheidt, T., Bernfur, K., Vendruscolo, M., Dobson, C. M., Cohen, S. I. A., Šileikis, E., Lundqvist, M., Qian, F., O’Malley, T. T., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0505-6 · Cited by 201 · see citing works
Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery
Pardridge, W. M. (2020) · Pharmaceuticals · doi:10.3390/ph13110394 · Cited by 193 · see citing works
TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance
Xiang, X., Werner, G., Bohrmann, B., Liesz, A., Mazaheri, F., Capell, A., Feederle, R., Knuesel, I., Kleinberger, G., & Haass, C. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606370 · Cited by 183 · see citing works
“For in vitro and ex vivo phagocytosis assay, the following antibodies were used: rat monoclonal antibody 2D8 against Ab1–16 (Shirotani et al, 2007), rabbit polyclonal antibody 6687 against cytosolic domain of APP (Capell et al, 2000), mouse IgG2a isotype control (Sigma-Aldrich), and mouse monoclonal mAb11 (IgG2a (Bohr…”
InfluentialSelf-citationGoure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt272 · Cited by 190 · see citing works
“In a chronic treatment study in 5- to 6-month-old PS2APP transgenic mice, gantenerumab caused a significant reduction in preexisting small plaques; however, there was an increase in larger plaques [215].”
BackgroundInfluentialTargeting microglia for the treatment of Alzheimer’s Disease
Wes, P. D., Sayed, F. A., Bard, F., & Gan, L. (2016) · Glia · doi:10.1002/glia.22988 · Cited by 185 · see citing works
“…microglia in an ex vivo assay with brain sections from PDAPP mice or AD tissue was dependent on the antibody effector function (Bard et al., 2000b; Bohrmann et al., 2012); (2) in mice, antibody isotypes with high affinity for FcgRs, such as mouse IgG2a, were more efficacious than lower affinity…”
BackgroundAnti-amyloid antibody therapies in Alzheimer's disease
Perneczky, R., Jessen, F., Grimmer, T., Levin, J., Flöel, A., Peters, O., & Froelich, L. (2023) · Brain · doi:10.1093/brain/awad005 · Cited by 182 · see citing works
Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178 · see citing works
“2nM) than Aβ monomers (17nM).(45) A 2-year, double-blind, placebo-controlled, phase II/III study (SCarlet RoAD) investigating gantenerumab in 797 Aβ-PET–positive prodromal AD patients was prematurely halted for failure to demonstrate efficacy, despite dose-dependent reductions in brain amyloid (PET) and CSF tau parame…”
BackgroundTargeting Amyloid Aggregation: An Overview of Strategies and Mechanisms
Giorgetti, S., Greco, C., Tortora, P., & Aprile, F. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092677 · Cited by 174 · see citing works
“Crenezumab Monoclonal antibody Aβ AD [72] Gantenerumab Monoclonal antibody Aβ AD [73] Solanezumab **** Monoclonal antibody Aβ AD [74] Tanshinones Diterpene Aβ AD [75] Dopamine and L-dopa Neurotransmitter Aβ/α-syn/IAPP AD/PD/diabetes [76,77] Methylene Blue Thiazine dye tau/PrP/ Aβ AD [55,78,79]”
BackgroundGrimm, H. P., Schumacher, V. L., Schäfer, M. K.-H., Imhof-Jung, S., Freskgård, P., Brady, K., Hofmann, C., Rüger, P., Schlothauer, T., Göpfert, U., et al. (2023) · mAbs · doi:10.1080/19420862.2023.2261509 · Cited by 173 · see citing works
“Multiple therapeutic antibodies are currently under clinical investigation, which have mechanisms of action (MoAs) involving targeted amyloid-beta (Aβ) binding, recruitment of microglia via the antibody’s wild-type Fc domain binding to Fc gamma receptors, and Fc-mediated antibody – Aβ complex clearance.(9,10) However,…”
BackgroundImmunotherapy for Alzheimer’s disease: hoops and hurdles
Lemere, C. A. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-36 · Cited by 196 · see citing works
Amyloid‐ß‐directed immunotherapy for Alzheimer's disease
Lannfelt, L., Relkin, N. R., & Siemers, E. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12168 · Cited by 157 · see citing works
Passive immunotherapies targeting Aβ and tau in Alzheimer's disease
Plotkin, S. S., & Cashman, N. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105010 · Cited by 156 · see citing works
Anti-Amyloid Immunotherapies for Alzheimer's Disease: A 2023 Clinical Update
Yadollahikhales, G., & Rojas, J. C. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01405-0 · Cited by 162 · see citing works
Kim, B., Kim, S., Nam, Y., Park, Y., Shin, S. M., & Moon, M. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00465-w · Cited by 150 · see citing works
Rosenberg, R. N., Lambracht‐Washington, D., Yu, G., & Xia, W. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0301 · Cited by 145 · see citing works
Cogswell, P. M., Barakos, J. A., Barkhof, F., Benzinger, T. L. S., Jack, C. R., Poussaint, T. Y., Raji, C. A., Ramanan, V. K., & Whitlow, C. T. (2022) · American Journal of Neuroradiology · doi:10.3174/ajnr.a7586 · Cited by 146 · see citing works
“Risk factors for ARIA are drug exposure, APOE-e4 allele carriership, and pretreatment microhemorrhages.(24,27,37,38) Regarding drug exposure, the risk of ARIA was”
BackgroundFibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
Sebastian Monasor, L., Müller, S. A., Colombo, A. V., Tanrioever, G., König, J., Roth, S., Liesz, A., Berghofer, A., Piechotta, A., Prestel, M., et al. (2020) · eLife · doi:10.7554/elife.54083 · Cited by 147 · see citing works
“…a therapeutic approach since substantial reduction of Aβ burden appears to correlate with cognitive benefits (Bacskai et al., 2001; Bard et al., 2000; Bohrmann et al., 2012; Janus et al., 2000; Lathuiliere et al., 2016; Morgan et al., 2000; Nicoll et al., 2006; Nicoll et al., 2003; Schenk et al.,…”
BackgroundTherapeutic Strategies Targeting Amyloid-β in Alzheimer’s Disease
Pinheiro, L. M. V., & Faustino, C. M. C. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321163438 · Cited by 142 · see citing works
Zhao, P., Xu, Y., Jiang, L., Fan, X., Li, L., Li, X., Arase, H., Zhao, Y., Cao, W., Zheng, H., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abq0095 · Cited by 141 · see citing works
Ovais, M., Zia, N., Ahmad, I., Khalil, A., Raza, A., Ayaz, M., Sadiq, A., Ullah, F., & Shinwari, Z. K. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00284 · Cited by 120 · see citing works
Pardridge, W. M. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.952627 · Cited by 152 · see citing works
Drug development for alzheimer’s disease: Microglia induced neuroinflammation as a target
Dong, Y., Li, X., Cheng, J., & Hou, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030558 · Cited by 136 · see citing works
Miles, L. A., Crespi, G. A. N., Doughty, L., & Parker, M. W. (2013) · Scientific Reports · doi:10.1038/srep01302 · Cited by 130 · see citing works
Awasthi, M., Singh, S., Pandey, V. P., & Dwivedi, U. N. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.01.008 · Cited by 135 · see citing works
Valera, E., Spencer, B. J., & Masliah, E. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0397-z · Cited by 129 · see citing works
Biometals and Their Therapeutic Implications in Alzheimer's Disease
Ayton, S., Lei, P., & Bush, A. I. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0312-z · Cited by 132 · see citing works
“Gantenerumab was shown to bind to cerebral Aβ in APP/presenilin 1 (PS1) transgenic mouse model, to reduce amyloid burden in mouse brain, and to prevent the formation of new plaque [19].”
BackgroundImmunotherapy for neurodegenerative diseases: Focus on α-synucleinopathies
Valera, E., & Masliah, E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.013 · Cited by 132 · see citing works
Huang, M., Hu, M., Song, Q., Song, H., Huang, J., Gu, X., Wang, X., Chen, J., Kang, T., Feng, X., et al. (2015) · ACS Nano · doi:10.1021/acsnano.5b03124 · Cited by 127 · see citing works
Uddin, M. S., Kabir, M. T., Rahman, M. S., Behl, T., Jeandet, P., Ashraf, G. M., Najda, A., Bin-Jumah, M. N., El-Seedi, H. R., & Abdel‐Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165858 · Cited by 127 · see citing works
“The most probable mechanism of the effects of this antibody seems to be the binding to small plaques and stimulation of a phagocytic response by microglia [247].”
BackgroundMajdi, A., Sadigh‐Eteghad, S., Aghsan, S. R., Farajdokht, F., Vatandoust, S. M., Abbas-Abad, A. N., & Mahmoudi, J. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0089 · Cited by 124 · see citing works
Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin
Ultsch, M., Li, B., Maurer, T., Mathieu, M., Adolfsson, O., Muhs, A., Pfeifer, A., Pihlgren, M., Bainbridge, T. W., Reichelt, M., et al. (2016) · Scientific Reports · doi:10.1038/srep39374 · Cited by 124 · see citing works
Zou, Y. F., Qian, Z., Chen, Y., Qian, H., Wei, G., & Zhang, Q. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00537 · Cited by 120 · see citing works
Leveraging preclinical models for the development of Alzheimer disease therapeutics
Scearce-Levie, K. A., Sanchez, P. E., & Lewcock, J. W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0065-9 · Cited by 118 · see citing works
Donanemab (LY3002813) dose‐escalation study in Alzheimer's disease
Lowe, S. L., Willis, B. A., Hawdon, A., Natanegara, F., Chua, L., Foster, J., Shcherbinin, S., Ardayfio, P. A., & Sims, J. R. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12112 · Cited by 118 · see citing works
Lowe, S. L., Evans, C. D., Shcherbinin, S., Cheng, Y.-J., Willis, B. A., Gueorguieva, I., Lo, A., Fleisher, A., Dage, J. L., Ardayfio, P. A., et al. (2021) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2021.56 · Cited by 119 · see citing works
Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges
Pais, M. V., Martinez, L. D., Ribeiro, O. G., Loureiro, J. C., Fernandez, R., Valiengo, L. D. C. L., Canineu, P. R., Stella, F., Talib, L. L., Radanovic, M., et al. (2020) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2019-0735 · Cited by 118 · see citing works
Zhan, C., Chen, Y., Tang, Y., & Wei, G. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00277 · Cited by 115 · see citing works
Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice
Kastanenka, K. V., Bussière, T., Shakerdge, N. B., Qian, F., Weinreb, P. H., Rhodes, K., & Bacskai, B. J. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2080-16.2016 · Cited by 112 · see citing works
“However, studies with anti-A immunotherapy have led to conflicting results, with effects on parenchymal A often accompanied by no or very minor reversal of memory deficits (Arendash et al., 2001, Austin et al., 2003, Adolfsson et al., 2012, Bohrmann et al., 2012).”
ResultCentral nervous system myeloid cells as drug targets: current status and translational challenges
Biber, K. P. H., Möller, T., Boddeke, E., & Prinz, M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.14 · Cited by 111 · see citing works
Bateman, R. J., Cummings, J., Schobel, S., Salloway, S., Vellas, B., Boada, M., Black, S. E., Blennow, K., Fontoura, P., Klein, G., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01110-8 · Cited by 109 · see citing works
Weber, F. C., Bohrmann, B., Niewoehner, J., Fischer, J. A. A., Rueger, P., Tiefenthaler, G., Moelleken, J., Bujotzek, A., Brady, K., Singer, T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.019 · Cited by 105 · see citing works
Self-citationSpecific Uptake of an Amyloid-β Protofibril-Binding Antibody-Tracer in AβPP Transgenic Mouse Brain
Magnusson, K., Sehlin, D., Syvänen, S., Svedberg, M. M., Philipson, O., Söderberg, L., Tegerstedt, K., Holmquist, M., Gellerfors, P., Максимилианович, Т. В., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130029 · Cited by 105 · see citing works
Folch, J., Ettcheto, M., Petrov, D., Abad, S., Pedrós, I., Marin, M., Olloquequi, J., & Camins, A. (2017) · Neurología (English Edition) · doi:10.1016/j.nrleng.2015.03.019 · Cited by 104 · see citing works
Anti-Amyloid Therapies for Alzheimer’s Disease and the Amyloid Cascade Hypothesis
Fedele, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914499 · Cited by 102 · see citing works
“The antibody recognises both N-terminal and central regions of the peptide and induces its removal by Fc receptor-mediated microglial phagocytosis [59,60].”
BackgroundPassive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?
Moreth, J., Mavoungou, C., & Schindowski, K. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-18 · Cited by 100 · see citing works
Immunotherapy for Alzheimer's disease
Wısnıewskı, T., & Goñi, F. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.020 · Cited by 99 · see citing works
Panza, F., Solfrizzi, V., Imbimbo, B. P., Tortelli, R., Santamato, A., & Logroscino, G. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.883921 · Cited by 97 · see citing works
Amyloid-Related Imaging Abnormalities: An Update
Roytman, M., Mashriqi, F., Al-Tawil, K., Schulz, P. E., Zaharchuk, G., Benzinger, T. L. S., & Franceschi, A. M. (2023) · American Journal of Roentgenology · doi:10.2214/ajr.22.28461 · Cited by 99 · see citing works
Is there still any hope for amyloid-based immunotherapy for Alzheimer's disease?
Panza, F., Logroscino, G., Imbimbo, B. P., & Solfrizzi, V. (2014) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000041 · Cited by 98 · see citing works
“In transgenic mice, gantenerumab significantly reduced the amyloid plaque burden by recruiting microglia and preventing new senile plaque formation without altering plasma Ab [74].”
BackgroundFolch, J., Ettcheto, M., Petrov, D., Abad, S., Pedrós, I., Marin, M., Olloquequi, J., & Camins, A. (2015) · Neurología · doi:10.1016/j.nrl.2015.03.012 · Cited by 98 · see citing works
Jacobsen, H., Ozmen, L., Caruso, A., Narquizian, R., Hilpert, H., Jacobsen, B., Terwel, D., An, T.-H., & Bohrmann, B. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1405-14.2014 · Cited by 93 · see citing works
“(Bohrmann et al., 2012) was significantly enhanced by combination treatment.”
BackgroundMethodInfluentialSelf-citationMolecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies
Crespi, G. A. N., Hermans, S. J., Parker, M. W., & Miles, L. A. (2015) · Scientific Reports · doi:10.1038/srep09649 · Cited by 96 · see citing works
Advances in Alzheimer’s Disease Drug Development
Rafii, M. S., & Aisen, P. S. S. (2015) · BMC Medicine · doi:10.1186/s12916-015-0297-4 · Cited by 95 · see citing works
BACE inhibitors in clinical development for the treatment of Alzheimer’s disease
Panza, F., Lozupone, M., Solfrizzi, V., Sardone, R., Piccininni, C., Dibello, V., Stallone, R., Giannelli, G., Bellomo, A., Greco, A., et al. (2018) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1531706 · Cited by 92 · see citing works
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
Buccellato, F. R., D’Anca, M., Tartaglia, G. M., Del Fabbro, M., Scarpini, E., & Galimberti, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813900 · Cited by 94 · see citing works
Surowka, M., Schäfer, W. M., & Klein, C. (2021) · mAbs · doi:10.1080/19420862.2021.1967714 · Cited by 92 · see citing works
Amyloid-related Imaging Abnormalities in Alzheimer Disease Treated with Anti–Amyloid-β Therapy
Agarwal, A., Gupta, V., Brahmbhatt, P., Desai, A., Vibhute, P., Joseph-Mathurin, N., & Bathla, G. (2023) · RadioGraphics · doi:10.1148/rg.230009 · Cited by 90 · see citing works
Uhlmann, R. E., Rother, C., Rasmussen, J., Schelle, J., Bergmann, C., Ullrich Gavilanes, E. M., Fritschi, S. K., Buehler, A., Baumann, F., Skodras, A., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00737-w · Cited by 87 · see citing works
Critical Appraisal of Amyloid Lowering Agents in AD
Decourt, B., Boumelhem, F., Pope, E. D., Shi, J., Mari, Z. K., & Sabbagh, M. N. (2021) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-021-01125-y · Cited by 85 · see citing works
Open questions for Alzheimer’s disease immunotherapy
Golde, T. E. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt233 · Cited by 85 · see citing works
“Pittsburgh Compound B) scans [33,34].”
Alzheimer’s Disease: A Brief History of Immunotherapies Targeting Amyloid β
Vogt, A. S., Jennings, G. T., Mohsen, M. O., Vogel, M., & Bachmann, M. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043895 · Cited by 86 · see citing works
Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?
Mahgoub, N., & Alexopoulos, G. S. (2016) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2015.12.003 · Cited by 81 · see citing works
“Gantenerumab induced cellular phagocytosis of human amyloid-β deposits in AD brain (70).”
Claes, C., Daele, J. V. D., Boon, R., Schouteden, S., Colombo, A. V., Monasor, L. S., Fiers, M. W. E. J., Ordovás, L., Nami, F., Bohrmann, B., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.09.006 · Cited by 81 · see citing works
Self-citationLoeffler, D. A. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230025 · Cited by 86 · see citing works
Islet amyloid polypeptide: Another key molecule in Alzheimer’s pathogenesis?
Zhang, Y., & Song, W. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.03.001 · Cited by 78 · see citing works
“…clinical trials since 2000 including both active vaccinations (e.g. CAD 106 and Affitope AD02) (Farlow et al., 2015; Schneeberger et al., 2010, 2009; Winblad et al., 2012) and passive vaccinations (e.g. solanezumab and gantenerumab) (Bohrmann et al., 2012; Farlow et al., 2012; Uenaka et al., 2012).”
BackgroundBiomarkers in Amyloid-β Immunotherapy Trials in Alzheimer’s Disease
Blennow, K., Hampel, H. J., & Zetterberg, H. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.154 · Cited by 79 · see citing works
- Authors
- Bohrmann, B., Baumann, K., Benz, J., Gerber, F., Huber, W., Knoflach, F., Messer, J., Oroszlan, K., Rauchenberger, R., Richter, W. F., Rothe, C., Urban, M., Bardroff, M., Winter, M., Nordstedt, C., & Loetscher, H.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- F. Hoffmann-La Roche Ltd., pRED, Basel, Switzerland
- MorphoSys (Germany) (DE)
- Corresponding author
- Bohrmann, Bernd
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2012-01-12
- Volume
- 28
- Issue
- 1
- Pages
- 49-69
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1927066019
- Cited by
- 448
- References
- 61
- Citations by year
- 2026: 21 · 2025: 32 · 2024: 49 · 2023: 43 · 2022: 43 · 2021: 26 · 2020: 45 · 2019: 29 · 2018: 29 · 2017: 23 · 2016: 31 · 2015: 21 · 2014: 31 · 2013: 19 · 2012: 5
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- 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
- gantenerumab, anti-amyloid beta antibodies
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Cerebral Cortex, Cricetulus, Female, Cricetinae, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Phagocytosis, Protein Binding, Amyloid beta-Peptides, CHO Cells, Rats, Sprague-Dawley, Protein Structure, Tertiary, Crystallography, X-Ray, Excitatory Postsynaptic Potentials, Mice, Rats, Antibodies, Monoclonal, Humanized
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
