Target engagement in an Alzheimer trial: crenezumab lowers amyloid β oligomers in cerebrospinal fluid
Open accessAbstract
OBJECTIVE: Oligomeric forms of amyloid β protein (oAβ) are believed to be principally responsible for neurotoxicity in Alzheimer disease (AD), but it is not known whether anti-Aβ antibodies are capable of lowering oAβ levels in humans. METHODS: We developed an ultrasensitive immunoassay and used it to measure oAβ in cerebrospinal fluid (CSF) from 104 AD subjects participating in the ABBY and BLAZE phase 2 trials of the anti-Aβ antibody crenezumab. Patients received subcutaneous (SC) crenezumab (300mg) or placebo every 2 weeks, or intravenous (IV) crenezumab (15mg/kg) or placebo every 4 weeks for 68 weeks. Ninety-eight of the 104 patients had measurable baseline oAβ levels, and these were compared to levels at week 69 in placebo (n = 28), SC (n = 35), and IV (n = 35) treated patients. RESULTS: Among those receiving crenezumab, 89% of SC and 86% of IV patients had lower levels of oAβ at week 69 versus baseline. The difference in the proportion of patients with decreasing levels was significant for both treatment arms: p = 0.0035 for SC and p = 0.01 for IV crenezumab versus placebo. The median percentage change was -48% in the SC arm and -43% in the IV arm. No systematic change was observed in the placebo group, with a median change of -13% and equivalent portions with negative and positive change. INTERPRETATION: Crenezumab lowered CSF oAβ levels in the large majority of treated patients tested. These results support engagement of the principal pathobiological target in AD and identify CSF oAβ as a novel pharmacodynamic biomarker for use in trials of anti-Aβ agents. ANN NEUROL 2019;86:215-224.
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Crenezumab, gantenerumab, and solanezumab are major therapies enrolled for preclinical studies or for at-risk populations, and are also studied in prodromal and very mild Alzheimer's disease patients.
“Crenezumab, gantenerumab, and solanezumab are the major therapies that are enrolled for preclinical studies or for at-risk populations, while crenezumab, gantenerumab, and solanezumab are the drugs that are for studies in prodromal and very mild AD patients (Yang et al., 2019).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Yang et al., 2019
Many ongoing mAbs trials are in phase 3, including crenezumab, gantenerumab, and solanezumab in studies for preclinical or at-risk populations.
“and crenezumab,70 gantenerumab, and solanezumab71 in studies for preclinical or at-risk populations”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [71]
First results from aducanumab and BAN2401 trials suggested a treatment-related reduction in cerebral amyloid burden in agreement with deceleration of cognitive decline in patients with prodromal and very mild AD.
“First results from aducanumab and BAN2401 trials suggested, at first, a treatment-related result of reducing in cerebral amyloid burden in agreement to deceleration of cognitive decline in patients with prodromal and very mild AD.71,72”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [71]
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Cites
Clinical and biomarker changes in dominantly inherited Alzheimer's disease
Bateman, R. J., Xiong, C., Benzinger, T. L. S., Fagan, A. M., Goate, A., Fox, N. C., Marcus, D. S., Cairns, N. J., Xie, X., Blazey, T. M., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1202753 · Cited by 3,814 · see citing works
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
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
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · see citing works
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870 · see citing works
The A4 Study: Stopping AD Before Symptoms Begin?
Sperling, R. A., Rentz, D. M., Johnson, K. A., Karlawish, J. H., Donohue, M., Salmon, D. P., & Aisen, P. S. S. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007941 · Cited by 756 · see citing works
Johnson‐Wood, K., Lee, M., Motter, R. N., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M. N., Tan, H. T., Games, D., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1550 · Cited by 634 · see citing works
Testing the Right Target and Right Drug at the Right Stage
Sperling, R. A., Jack, C. R., & Aisen, P. S. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002609 · Cited by 550 · see citing works
Bittner, T., Zetterberg, H., Teunissen, C. E., Ostlund, R. E., Militello, M., Andreasson, U., Hubeek, I., Gibson, D., Chu, D. C., Eichenlaub, U., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.09.009 · Cited by 374 · see citing works
Yang, T., Li, S., Xu, H., Walsh, D. M., & Selkoe, D. J. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.1698-16.2016 · Cited by 347 · see citing works
Adolfsson, O., Pihlgren, M., Toni, N., Varisco, Y., Buccarello, A. L., Antoniello, K., Lohmann, S., Piorkowska, K., Gafner, V., Atwal, J. K., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4742-11.2012 · Cited by 317 · see citing works
Ultrasensitive Flow-based Immunoassays Using Single-Molecule Counting
Todd, J., Freese, B., Lu, A., Held, D., Morey, J., Livingston, R., & Goix, P. J. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.091181 · Cited by 289 · see citing works
Cummings, J. L., Cohen, S., van Dyck, C. H., Brody, M., Curtis, C. T., Cho, W., Ward, M. E., Friesenhahn, M. J., Rabe, C., Brunstein, F., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000005550 · Cited by 254 · see citing works
A Sensitive Aβ Oligomer Assay Discriminates Alzheimer's and Aged Control Cerebrospinal Fluid
Savage, M. J., Kalinina, J., Wolfe, A. L., Tugusheva, K., Korn, R., Cash-Mason, T., Maxwell, J. W., Hatcher, N. G., Haugabook, S. J., Wu, G., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1675-13.2014 · Cited by 183 · see citing works
Hong, W., Wang, Z., Liu, W., O’Malley, T. T., Jin, M., Willem, M., Haass, C., Frosch, M. P., & Walsh, D. M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1846-7 · Cited by 166 · see citing works
Salloway, S., Honigberg, L. A., Cho, W., Ward, M. E., Friesenhahn, M. J., Brunstein, F., Quartino, A. L., Clayton, D., Mortensen, D. L., Bittner, T., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0424-5 · Cited by 151 · 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
Yang, T., O’Malley, T. T., Kanmert, D., Jerecı̀ć, J., Zieske, L. R., Zetterberg, H., Hyman, B. T., Walsh, D. M., & Selkoe, D. J. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0100-y · Cited by 115 · see citing works
An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer’s disease
Jin, M., O’Nuallain, B., Hong, W., Boyd, J. D., Lagomarsino, V. N., O’Malley, T. T., Liu, W., Vanderburg, C. R., Frosch, M. P., Young‐Pearse, T. L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05068-w · Cited by 70 · see citing works
O’Malley, T. T., Oktaviani, N. A., Zhang, D., Lomakin, A., O’Nuallain, B., Linse, S. S., Benedek, G. B., Rowan, M. J., Mulder, F. A. A., & Walsh, D. M. (2014) · Biochemical Journal · doi:10.1042/bj20140219 · Cited by 67 · see citing works
Mably, A. J., Liu, W., Donald, J. M. M., Dodart, J., Bard, F., Lemere, C. A., O’Nuallain, B., & Walsh, D. M. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.07.008 · Cited by 52 · see citing works
Feinberg, H., Saldanha, J. W., Diep, L., Goel, A. S., Widom, A., Veldman, G. M., Weis, W. I., Schenk, D., & Basi, G. S. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt261 · Cited by 52 · see citing works
Lu, Y.-S., Riddell, D., Hajós-Korcsok, É., Bales, K., Wood, K. M., Nolan, C., Robshaw, A., Zhang, L.-M., Leung, L. Y., Becker, S. L., et al. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.192625 · Cited by 37 · see citing works
Swanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J. M., Lai, R. Y. K., Lannfelt, L., Kramer, L. D., & Luthman, J. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.07.009 · Cited by 28 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [26]Swanson CJ, Zhang Y, Dhadda S, et al. Treatment of early AD subjects with BAN2401, an antiti‐Aß protofibril monoclonnal antibody, significantly clears amyloid plaque and reduces clinical decline. Abstract presented at: Alzheimer's Association International Conference; July 22–26, 2018; Chicago, IL.
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Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966 · see citing works
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Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
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Ke, P. C., Zhou, R., Serpell, L. C., Riek, R., Knowles, T. P. J., Lashuel, H. A., Gazit, E., Hamley, I. W., Davis, T. P., Fändrich, M., et al. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00199a · Cited by 567 · see citing works
Alzheimer’s disease drug development pipeline: 2020
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12050 · Cited by 557 · see citing works
Alzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547 · see citing works
The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis
Tolar, M., Abushakra, S., & Sabbagh, M. (2020) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.09.075 · Cited by 275 · 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
The Neurovascular Unit Dysfunction in Alzheimer’s Disease
Soto-Rojas, L. O., Pacheco‐Herrero, M., Martínez-Gómez, P. A., Campa-Córdoba, B. B., Apátiga-Pérez, R., Villegas-Rojas, M. M., Harrington, C. R., de la Cruz, F., Garcés‐Ramírez, L., & Luna‐Muñoz, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042022 · Cited by 140 · see citing works
An update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122 · see citing works
Kulenkampff, K., Perez, A.-M. W., Sormanni, P., Habchi, J., & Vendruscolo, M. (2021) · Nature Reviews Chemistry · doi:10.1038/s41570-021-00254-9 · Cited by 110 · see citing works
Immunotherapies for Neurodegenerative Diseases
Mortada, I., Farah, R., Nabha, S. M., Ojcius, D. M., Fares, Y., Almawi, W. Y., & Sadier, N. S. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.654739 · Cited by 112 · see citing works
New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease
Zhang, F., Zhong, R.-J., Cheng, C., Li, S., & Le, W.-D. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00565-5 · Cited by 105 · see citing works
Rational design of a conformation-specific antibody for the quantification of Aβ oligomers
Aprile, F. A., Sormanni, P., Podpolny, M., Chhangur, S., Needham, L.-M., Ruggeri, F. S., Perni, M., Limbocker, R., Heller, G. T., Šneideris, T., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1919464117 · Cited by 99 · see citing works
Loeffler, D. A. (2023) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230025 · Cited by 86 · see citing works
Guthrie, H., Honig, L., Lin, H., Sink, K., Blondeau, K., Quartino, A., Dolton, M., Carrasco-Triguero, M., Lian, Q., Bittner, T., et al. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200134 · Cited by 48 · see citing works
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Raut, S., Bhalerao, A., Powers, M., Gonzalez, M., Mancuso, S., & Cucullo, L. (2023) · Cells · doi:10.3390/cells12162019 · Cited by 65 · see citing works
Ghosh, S., Durgvanshi, S., Agarwal, S., Raghunath, M., & Sinha, J. K. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200429011823 · Cited by 57 · see citing works
Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer’s Disease Therapeutics
Jeong, H., Shin, H., Hong, S., & Kim, Y. S. (2022) · Experimental Neurobiology · doi:10.5607/en22004 · Cited by 56 · see citing works
Zu, L., Wang, X., Liu, P., Xie, J., Zhang, X., Liu, W., Li, Z., Zhang, S., Li, K., Giannetti, A. E., et al. (2024) · Advanced Science · doi:10.1002/advs.202308783 · Cited by 57 · see citing works
Insights into the use of biomarkers in clinical trials in Alzheimer's disease
Pascoal, T. A., Aguzzoli, C. S., Lussier, F. Z., Crivelli, L., Suemoto, C. K., Fortea, J., Rosa‐Neto, P., Zimmer, E. R., Ferreira, P. C. L., & Bellaver, B. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105322 · Cited by 55 · see citing works
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Song, M., Zhao, X., & Song, F. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02248-y · Cited by 56 · see citing works
Morató, X., Pytel, V., Jofresa, S., Ruiz, A., & Boada, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169305 · Cited by 53 · see citing works
Mukherjee, S., Perez, K. A., Lago, L., Klatt, S., McLean, C., Birchall, I. E., Barnham, K. J., Masters, C. L., & Roberts, B. R. (2021) · Brain Communications · doi:10.1093/braincomms/fcab028 · Cited by 50 · see citing works
An ultra‐sensitive immunoassay detects and quantifies soluble Aβ oligomers in human plasma
Liu, L., Kwak, H., Lawton, T., Jin, S., Meunier, A. L., Dang, Y., Ostaszewski, B. L., Pietras, A., Stern, A. M., & Selkoe, D. J. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12457 · Cited by 49 · see citing works
Kaur, P., Khera, A., Alajangi, H. K., Sharma, A., Jaiswal, P. K., Singh, G., & Barnwal, R. P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03164-z · Cited by 53 · see citing works
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Li, S., & Stern, A. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01589-5 · Cited by 46 · see citing works
Yoshida, K. J., Moein, A., Bittner, T., Ostrowitzki, S., Lin, H. H., Honigberg, L. A., Jin, J. Y., & Quartino, A. L. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-0580-2 · Cited by 48 · see citing works
Ayton, S., & Bush, A. I. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101212 · Cited by 45 · see citing works
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Kreiser, R. P., Wright, A. K., Block, N. R., Hollows, J. E., Nguyen, L. T., LeForte, K., Mannini, B., Vendruscolo, M., & Limbocker, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228651 · Cited by 47 · see citing works
Meilandt, W. J., Maloney, J. A., Imperio, J., Lalehzadeh, G., Earr, T., Crowell, S., Bainbridge, T. W., Lu, Y., Ernst, J. A., Fuji, R. N., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0553-5 · Cited by 45 · see citing works
Liu, Y., Wang, J., Li, Q., Fowler, C. J., Zeng, F., Deng, J., Xu, Z., Zhou, H., Doecke, J. D., Villemagne, V. L., et al. (2021) · Science Advances · doi:10.1126/sciadv.abb0457 · Cited by 44 · see citing works
Newer Therapeutic Approaches in Treating Alzheimer’s Disease: A Comprehensive Review
Sree, R. R., Kalyan, M., Anand, N., Mani, S., Gorantla, V. R., Sakharkar, M. K., Song, B., & Chidambaram, S. B. (2025) · ACS Omega · doi:10.1021/acsomega.4c05527 · Cited by 45 · see citing works
Liu, J., Wang, Y., Jing, G., Sun, J., & Qinfeng, S. (2020) · Aging · doi:10.18632/aging.103306 · Cited by 41 · see citing works
Tondo, G., Marchi, F. D., Bonardi, F., Menegon, F., Verrini, G., Aprile, D., Anselmi, M., Mazzini, L., & Comi, C. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13113098 · Cited by 43 · see citing works
Zhang, S.-S., Gao, Z., Feng, L., & Li, M. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s483412 · Cited by 38 · see citing works
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Rationale for the development of an Alzheimer’s disease vaccine
Kwan, P., Konno, H., Chan, K. Y., & Baum, L. (2019) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2019.1665453 · Cited by 34 · see citing works
Current and Emerging Pharmacological Targets for the Treatment of Alzheimer’s Disease
Morsy, A., & Trippier, P. C. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190744 · Cited by 34 · see citing works
Song, C., Zhang, T., & Zhang, Y. (2022) · Molecules · doi:10.3390/molecules27196751 · Cited by 31 · see citing works
Viola, K. L., Bicca, M. A., Bebenek, A. M., Kranz, D. L., Nandwana, V., Waters, E. A., Haney, C. R., Lee, M. Y., Gupta, A., Brahmbhatt, Z., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.768646 · Cited by 29 · see citing works
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Denis, H. L., David, L. S., & Cicchetti, F. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104569 · Cited by 30 · see citing works
Alzheimer Disease Clinical Trials Targeting Amyloid
Reiss, A. B., Montufar, N., DeLeon, J. R., Pinkhasov, A., Gomolin, I. H., Glass, A. D., Arain, H. A., & Stecker, M. M. (2021) · The Neurologist · doi:10.1097/nrl.0000000000000320 · Cited by 27 · see citing works
Dolton, M. J., Chesterman, A., Moein, A., Sink, K. M., Waitz, A., Blondeau, K., Kerchner, G. A., Hu, N., Brooks, L., Wetzel-Smith, M. K., et al. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2385 · Cited by 27 · see citing works
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Aljassabi, A., Zieneldien, T., Kim, J., Regmi, D., & Cao, C. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231163 · Cited by 25 · see citing works
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Hering, H., Bussière, T., Liu, C., Glajch, K. E., Weihofen, A., Grogan, J. L., & Walsh, D. M. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00872-7 · Cited by 26 · see citing works
Chen, Y., Wei, G., Zhao, J., Nussinov, R., & Ma, B. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00364 · Cited by 24 · see citing works
Chopra, G., Shabir, S., Yousuf, S., Kauts, S., Bhat, S. A., Mir, A. H., & Singh, M. P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03042-8 · Cited by 22 · see citing works
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Lozupone, M., Dibello, V., Sardone, R., Castellana, F., Zupo, R., Lampignano, L., Bortone, I., Stallone, R., Altamura, M., Bellomo, A., et al. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2348142 · Cited by 19 · see citing works
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Law, C. S. W., & Yeong, K. Y. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200312114223 · Cited by 17 · see citing works
The Development of Pharmacological Therapies for Alzheimer’s Disease
Ping, L., Sun, J., Cheng, Q., Yang, Y., Cordato, D. J., & Gao, J. (2021) · Neurology and Therapy · doi:10.1007/s40120-021-00282-z · Cited by 16 · see citing works
Perspective: Is therapeutic plasma exchange a viable option for treating Alzheimer's disease?
Imbimbo, B. P., Ippati, S., Ceravolo, F., & Watling, M. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12004 · Cited by 16 · see citing works
Recent advances in immunotherapy targeting amyloid-beta and tauopathies in Alzheimer’s disease
Sha, S., Ren, L., Xing, X., Guo, W., Wang, Y., Li, Y., Cao, Y., & Qu, L. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00846 · Cited by 16 · see citing works
Gautam, A. S., Pandey, S. K., Lasure, V., Dubey, S., & Singh, R. K. (2023) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2023.2227378 · Cited by 12 · see citing works
Feng, L., Wang, G., Song, Q., Feng, X., Su, J., Ji, G., & Li, M. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01330-3 · Cited by 11 · see citing works
Sharma, H. S., Muresanu, D. F., Nozari, A., Lafuente, J. V., Buzoianu, A. D., Sahib, S., Tian, Z. R., Bryukhovetskiy, I., Manzhulo, I., Menon, P. K., et al. (2021) · Progress in brain research · doi:10.1016/bs.pbr.2021.04.008 · Cited by 11 · see citing works
EPR Studies of Aβ42 Oligomers Indicate a Parallel In-Register β-Sheet Structure
Jang, C., Barron, D. P., Duo, L., Ma, C., Seabaugh, H., & Guo, Z. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00364 · Cited by 9 · see citing works
Amyloid-Directed Antibodies: Past, Present, and Future
Noorda, K., Noorda, K. J., Sabbagh, M. N., Bertelson, J. A., Singer, J., & Decourt, B. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240189 · Cited by 9 · see citing works
Imbimbo, B. P., Triaca, V., Imbimbo, C., & Nisticò, R. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.363185 · Cited by 9 · see citing works
Lecanamab Ushers in a New Era of Anti‐Amyloid Therapy for Alzheimer's Disease
Musiek, E. S., McDade, E., & Holtzman, D. M. (2023) · Annals of Neurology · doi:10.1002/ana.26643 · Cited by 9 · see citing works
Chen, S., Han, C., Wang, X., Zhang, Q., & Yang, X. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149203 · Cited by 7 · see citing works
Yang, T., Xu, Y. R., Jin, S., Ramalingam, N., Bellier, J., Lish, A. M., Ostaszewski, B. L., Young‐Pearse, T. L., Liu, L., Yang, H., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01802-x · Cited by 7 · see citing works
Jerom, J. P., Madhukumar, S., Nair, R. H., & Narayanan, S. P. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103802 · Cited by 7 · see citing works
Alzheimer’s disease and clinical trials
Paul, D., Agrawal, R., & Singh, S. (2024) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2023-0264 · Cited by 7 · see citing works
Wang, K., Na, L., & Duan, M. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200916123000 · Cited by 5 · see citing works
Spencer, J. I., Crane, M., Pisa, M., Waldman, A. D., & DeLuca, G. C. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.120056 · Cited by 5 · see citing works
Maheta, P., Patel, C. A., Parmar, D., Beladiya, J., Patel, S. K., Sheth, D. B., & Dholakia, S. P. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00540 · Cited by 4 · see citing works
Liu, Y., Chen, Y., & Fukui, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158428 · Cited by 4 · see citing works
Mondal, A. C., & Sushma (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666211228100955 · Cited by 4 · see citing works
Bittner, T., Duning, T., Rabe, C., Clayton, D., Quartino, A. L., Bohorquez, S. M. S., Hu, N., Rabbia, M. A., Shimizu, H., Eichenlaub, U., et al. (2020) · Clinical Neurophysiology · doi:10.1016/j.clinph.2019.12.038 · Cited by 4 · see citing works
Fluid Biomarkers in Clinical Trials for Alzheimer’s Disease: Current and Future Application
Yang, J.-W., Jia, L., Li, Y., Qiu, Q.-Q., Quan, M.-N., & Jia, J. (2021) · Journal of Alzheimer's Disease · doi:10.3233/jad-201068 · Cited by 6 · see citing works
Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies
Rathee, S., Pandey, V., Soni, S., Sen, D., & Jain, S. (2025) · Current Alzheimer Research · doi:10.2174/0115672050368798250626075628 · Cited by 5 · see citing works
Should we lower or raise levels of amyloid-β in the brains of Alzheimer patients?
Imbimbo, B. P., Ippati, S., Imbimbo, C., & Balducci, C. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106390 · Cited by 3 · see citing works
Chambers, M. J., Delport, A., & Hewer, R. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06229-9 · Cited by 3 · see citing works
Active immunization: A novel therapeutic strategy for treating Alzheimer's disease
Mazahir, F. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178288 · Cited by 2 · see citing works
“Current and emerging drug therapies in Alzheimer’s disease: A pathophysiological Perspective”
Aparajita, A., Jain, U., & Srivastava, P. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.11.078 · Cited by 2 · see citing works
The Diagnostic Potential of Circulating Autoantibodies to Amyloid-β in Alzheimer’s Disease
Xu, G.-Y., Liu, Y., Zeng, X., Chen, D., Zeng, G., Fan, D., Liu, Y.-H., & Wang, Y. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230252 · Cited by 1 · see citing works
Muthuraman, A., Ramesh, M., & Kumar, T. V. R. (2020) · Springer eBooks · doi:10.1007/978-981-15-5167-3_6
Customer Loyalty in E-Business.
Raggad, B. G., & Lawler, J. E. (2003) · International Conference on Enterprise Information Systems
Exploring the Efficacy of Anti-amyloid-β Therapeutics in Treating Alzheimer Disease
Downey, C. (2022) · Youth STEM Matters · doi:10.51892/ysm.1.202201
Action Mechanisms of Donepezil in Cardiac and Vascular Aspects: A ReviewPreprint
Shuang, Y., Dong, B., He, K., Peng, A., & Guo, L. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4645306
Chien, S.-C., Chang, C., Wang, H.-J., Hsu, C., Wang, Y., Chuang, C., & Chen, J.-C. (2025) · Sensing and Bio-Sensing Research · doi:10.1016/j.sbsr.2025.100805
Goswami, S., Verma, Y., & Rana, S. V. S. (2026) · Springer eBooks · doi:10.1007/978-981-95-5088-3_14
Multimerization of a rationally designed nanobody for enhanced avidity toward Aβ42 oligomers
Nowinska, M., Suh, E., Mogilevsky, C., & Vendruscolo, M. (2026) · Protein Science · doi:10.1002/pro.70754
- Authors
- Yang, T., Dang, Y., Ostaszewski, B., Mengel, D., Steffen, V., Rabe, C., Bittner, T., Walsh, D. M., & Selkoe, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Genentech (US)
- Corresponding author
- Walsh, Dominic M.
- Selkoe, Dennis J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2019-06-22
- Volume
- 86
- Issue
- 2
- Pages
- 215-224
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC6771589
- OpenAlex
- W2948149572
- Cited by
- 91
- References
- 26
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 11 · 2023: 11 · 2022: 14 · 2021: 16 · 2020: 22 · 2019: 5
- FWCI
- 9.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Harvard NeuroDiscovery Center
- Brigham and Women's Hospital
- National Institute on Aging (AG006173 (Selkoe), AG015739 (Selkoe), AG046275 (Wa)
- 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
- crenezumab, amyloid-beta oligomers, Alzheimer's disease, anti-amyloid antibodies, cerebrospinal fluid biomarkers, pharmacodynamic biomarkers, target engagement, subcutaneous administration, intravenous administration, immunoassay
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Biomarkers, Amyloid beta-Peptides, Drug Delivery Systems, Antibodies, Monoclonal, Humanized
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