The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
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.
Overview
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
Verification
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?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“| 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]
In the citing paper
“| 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]
In the citing paper
“| 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.
Citations
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,317
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1×
“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
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
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
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
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
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
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
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
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
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 765
“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).”
BackgroundThe 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
Clinical 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
Nguyen, P. H., Ramamoorthy, A., Sahoo, B. R., Zheng, J., Faller, P., Straub, J. E., Domínguez, L., Shea, J., Dokholyan, N. V., Simone, A. D., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01122 · Cited by 680
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
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
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 563
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
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
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
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
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 459
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
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
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
“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 420
“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
“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 369
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
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
BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease
Moussa‐Pacha, N. M., Abdin, S. M., Omar, H. A., Alniss, H., & Al‐Tel, T. H. (2020) · Medicinal Research Reviews · doi:10.1002/med.21622 · Cited by 274
Immunotherapeutic Approaches for Alzheimer’s Disease
Wisniewski, T., & Goñi, F. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.064 · Cited by 284
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 300
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 281
“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
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
“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
“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 244
“It binds both N-terminal and central amino acids of Aβ Phase III 225 mg SC [388]”
BackgroundA Historical Review of Brain Drug Delivery
Pardridge, W. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061283 · Cited by 219
Mullane, K., & Williams, M. J. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.11.014 · Cited by 219
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
“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).”
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
Kinetic 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 199
Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery
Pardridge, W. M. (2020) · Pharmaceuticals · doi:10.3390/ph13110394 · Cited by 198
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
“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
“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
“…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
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
“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 179
“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 180
“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
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 161
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 161
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 165
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 162
Rosenberg, R. N., Lambracht‐Washington, D., Yu, G., & Xia, W. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0301 · Cited by 149
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 150
“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
“…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 144
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
Ovais, M., Zia, N., Ahmad, I., Khalil, A. T., Raza, A., Ayaz, M., Sadiq, A., Ullah, F., & Shinwari, Z. K. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00284 · Cited by 140
Pardridge, W. M. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2014.952627 · Cited by 152
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
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 139
Valera, E., Spencer, B. J., & Masliah, E. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0397-z · Cited by 135
Miles, L. A., Crespi, G. A. N., Doughty, L., & Parker, M. W. (2013) · Scientific Reports · doi:10.1038/srep01302 · Cited by 130
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 134
“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].”
BackgroundHuang, 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
Immunotherapy 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
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 131
“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].”
BackgroundStructure 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
Majdi, 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 130
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
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 121
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
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 121
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 124
Green Tea Extracts EGCG and EGC Display Distinct Mechanisms in Disrupting Aβ42 Protofibril
Zhan, C., Chen, Y., Tang, Y., & Wei, G. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00277 · Cited by 115
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 111
“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
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
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 107
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 107
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 105
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
“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 103
Immunotherapy for Alzheimer's disease
Wısnıewskı, T., & Goñi, F. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.020 · Cited by 103
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 103
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
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 101
“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 102
Jacobsen, H., Ozmen, L., Caruso, A., Narquizian, R., Hilpert, H., Jacobsen, B., Terwel, D., Tanghe, A., & Bohrmann, B. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1405-14.2014 · Cited by 96
“(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
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 98
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
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
Surowka, M., Schäfer, W. M., & Klein, C. (2021) · mAbs · doi:10.1080/19420862.2021.1967714 · Cited by 96
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
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
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 87
Open questions for Alzheimer’s disease immunotherapy
Golde, T. E. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt233 · Cited by 87
“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 88
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
“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 88
Self-citationLoeffler, D. A. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230025 · Cited by 90
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 79
“…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 83
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
