11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study
Abstract
Background Carbon-11-labelled Pittsburgh compound B ((11)C-PiB) PET is a marker of cortical fibrillar amyloid-beta load in vivo. We used (11)C-PiB PET to investigate whether bapineuzumab, a humanised anti-amyloid-beta monoclonal antibody, would reduce cortical fibrillar amyloid-beta load in patients with Alzheimer's disease.Methods Patients with mild-to-moderate Alzheimer's disease were randomly assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to three in three ascending dose groups (0.5, 1.0, or 2.0 mg/kg). Each dose group was enrolled after safety review of the previous group. Randomisation was by interactive voice response system; masking was achieved with numbered kit allocation. Patients, investigators, study site personnel, sponsor staff, and carers were masked to treatment. Patients received up to six infusions, 13 weeks apart, and had (11)C-PiB PET scans at baseline and at weeks 20, 45, and 78. The primary outcome was the difference between the pooled bapineuzumab group and the pooled placebo group in mean change from screening to week 78 in (11)C-PiB cortical to cerebellar retention ratio averaged across six cortical regions of interest. Analysis was by modified intention to treat. This study is registered with EudraCT, number 2004-004120-12; ISRCTN17517446.Findings 28 patients were assigned to bapineuzumab (n=20) or placebo (n=8). 19 patients in the bapineuzumab group and seven in the placebo group were included in the modified intention-to-treat analysis. Estimated mean (11)C-PiB retention ratio change from baseline to week 78 was -0.09 (95% CI -0.16 to -0.02; p=0.014) in the bapineuzumab group and 0.15 (95% CI 0.02 to 0.28; p=0.022) in the placebo group. Estimated mean difference in (11)C-PiB retention ratio change from baseline to week 78 between the bapineuzumab group and the placebo group was -0.24 (95% CI -0.39 to -0.09; p=0.003). Differences between the bapineuzumab group and the placebo group in the individual regions of interest were similar to the overall mean difference. Adverse events were typically mild to moderate in severity and transient. Two patients in the 2.0 mg/kg bapineuzumab group had transient cerebral vasogenic oedema.Interpretation Treatment with bapineuzumab for 78 weeks reduced cortical (11)C-PiB retention compared with both baseline and placebo. (11)C-PiB PET seems to be useful in assessing the effects of potential Alzheimer's disease treatments on cortical fibrillar amyloid-beta load in vivo.Funding Elan Pharmaceuticals and Wyeth Research.
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Several anti-Aβ monoclonal antibodies tested in clinical trials in AD patients significantly reduce load of fibrillar Aβ as demonstrated using PET Aβ imaging.
“Several anti-Aβ monoclonal antibodies (mAbs) have been tested in clinical trials in AD patients and were found to significantly reduce load of fibrillar Aβ as demonstrated using PET Aβ imaging [5–8].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [7]
In phase 2 clinical studies, bapineuzumab reduced cerebrospinal fluid phospho-tau in patients with mild-to-moderate Alzheimer's disease.
“In phase 2 clinical studies involving patients with mild-to-moderate Alzheimer’s disease, patients who received bapineuzumab, as compared with those who received placebo, had a greater reduction in amyloid on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and reduced cerebrospinal fluid phosphorylated tau (phospho-tau), suggesting target engagement”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [10]
In phase 2 clinical studies, bapineuzumab reduced amyloid on PIB-PET more than placebo in patients with mild-to-moderate Alzheimer's disease.
“In phase 2 clinical studies involving patients with mild-to-moderate Alzheimer’s disease, patients who received bapineuzumab, as compared with those who received placebo, had a greater reduction in amyloid on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and reduced cerebrospinal fluid phosphorylated tau (phospho-tau), suggesting target engagement”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [10]
The reduction in amyloid accumulation on PIB-PET in APOE ε4 carriers was smaller than that seen in phase 2 studies that included the 2.0 mg/kg dose.
“A decreased rate of accumulation of amyloid in the brain on PIB-PET was seen in APOE ε4 carriers who received bapineuzumab, but the difference was smaller than that seen in phase 2 studies, which included the 2.0-mg-per-kilogram dose.10”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [10]
One of the antibodies to Aβ appears to reduce plaque burden.
“One of these antibodies, which to date has not yet reported any post-hoc evidence of clinical efficacy in its phase 3 trials, appears to reduce plaque burden [253].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [253]
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · see citing works
Self-citationThe Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347 · see citing works
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · 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
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
Self-citationBard, 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
Self-citationHolmes, 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
Self-citationClinical 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
Self-citationPathological verification of ischemic score in differentiation of dementias
Rosen, W. G., Terry, R. D., Fuld, P. A., Katzman, R., & Peck, A. (1980) · Annals of Neurology · doi:10.1002/ana.410070516 · Cited by 1,273 · see citing works
Hammers, A., Allom, R. J., Koepp, M. J., Free, S. L., Myers, R., Lemieux, L., Mitchell, T. N., Brooks, D. J., & Duncan, J. S. (2003) · Human Brain Mapping · doi:10.1002/hbm.10123 · Cited by 1,270 · see citing works
Self-citationJack, C. R., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., Shiung, M. M., Gunter, J. L., Boeve, B. F., Kemp, B. J., et al. (2009) · Brain · doi:10.1093/brain/awp062 · Cited by 1,099 · see citing works
Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Mathis, C. A., Price, J. C., Tsopelas, N. D., Lopresti, B. J., Ziolko, S., Bi, W., Paljug, W. R., et al. (2008) · Brain · doi:10.1093/brain/awn016 · Cited by 933 · see citing works
Self-citationAlzheimer's Disease: Molecular Understanding Predicts Amyloid-Based Therapeutics
Selkoe, D. J., & Schenk, D. (2003) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.140248 · Cited by 816 · see citing works
Self-citationBlennow, K., Wallin, A., Ågren, H., Spenger, C., Siegfried, J., & Vanmechelen, E. (1995) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815140 · Cited by 789 · see citing works
Self-citationA phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753 · see citing works
Self-citationKinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B
Price, J. C., Klunk, W. E., Lopresti, B. J., Lu, X., Hoge, J. A., Ziolko, S. K., Holt, D. P., MELTZER, C. C., DeKosky, S. T., & Mathis, C. A. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600146 · Cited by 712 · see citing works
Self-citationDevelopment of Cognitive Instruments for Use in Clinical Trials of Antidementia Drugs
Mohs, R. C., Knopman, D. S., Petersen, R. C., Ferris, S. H., Ernesto, C., Grundman, M., Sano, M., Bieliauskas, L. A., Geldmacher, D., Clark, C. M., et al. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00003 · Cited by 693 · see citing works
Self-citationAndreasen, N., Hesse, C., Davidsson, P., Minthon, L., Wallin, A., Winblad, B., Vanderstichele, H., Vanmechelen, E., & Blennow, K. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.673 · Cited by 660 · see citing works
Self-citationTwo-year follow-up of amyloid deposition in patients with Alzheimer's disease
Engler, H., Forsberg, A., Almkvist, O., Blomquist, G., Larsson, E., Savitcheva, I., Wall, A. E., Ringheim, A., Långström, B., & Nordberg, A. K. (2006) · Brain · doi:10.1093/brain/awl178 · Cited by 614 · see citing works
Amyloid, hypometabolism, and cognition in Alzheimer disease: An [11C]PIB and [18F]FDG PET study
Edison, P., Archer, H. A., Hinz, R., Hammers, A., Pavese, N., Tai, Y. F., Hotton, G., Cutler, D., Fox, N., Kennedy, A., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000244749.20056.d4 · Cited by 518 · see citing works
Self-citationVanmechelen, E., Vanderstichele, H., Davidsson, P., Kerschaver, E. V., Perre, B. V. D., Sjögren, M. J. C., Andreasen, N. C., & Blennow, K. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01036-3 · Cited by 487 · see citing works
Self-citationMohs, R. C., Knopman, D. S., Petersen, R. C., Ferris, S. H., Ernesto, C., Grundman, M., Sano, M., Bieliauskas, L. A., Geldmacher, D., Clark, C., et al. (1997) · PubMed · Cited by 487 · see citing works
Self-citationKlunk, W. E., Wang, Y., Huang, G.-F., Debnath, M. L., Holt, D. P., & Mathis, C. A. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01232-2 · Cited by 457 · see citing works
Self-citationFox, N. C., Cousens, S., Scahill, R. I., Harvey, R. J., & Rossor, M. N. (2000) · Archives of Neurology · doi:10.1001/archneur.57.3.339 · Cited by 354 · see citing works
Self-citationKlunk, W. E., Jacob, R. F., & Mason, R. P. (1999) · Analytical Biochemistry · doi:10.1006/abio.1998.2933 · Cited by 310 · see citing works
Self-citationKlunk, W. E., Wang, Y., Huang, G.-F., Debnath, M. L., Holt, D. P., Shao, L., Hamilton, R. L., Ikonomović, M. D., DeKosky, S. T., & Mathis, C. A. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02086.2003 · Cited by 305 · see citing works
Self-citationVellas, 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
Self-citationA Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials
Harrison, J., Minassian, S. L., Jenkins, L., Black, R. S., Koller, M., & Grundman, M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.9.1323 · Cited by 225 · see citing works
Self-citationIn VitroCharacterization of Pittsburgh Compound-B Binding to Lewy Bodies
Fodero‐Tavoletti, M. T., Smith, D. P., McLean, C., Adlard, P. A., Barnham, K. J., Foster, L. E., Leone, L., Perez, K. A., Cortés, M., Culvenor, J. G., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0630-07.2007 · Cited by 157 · see citing works
Immunotherapy Reduces Vascular Amyloid- in PDAPP Mice
Schroeter, S., Khan, K., Barbour, R., Doan, M., Chen, M., Guido, T., Gill, D., Basi, G., Schenk, D., Seubert, P., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2377-07.2008 · Cited by 133 · see citing works
Self-citationFunctional Disability in Alzheimer's Disease
Gauthier, S. G., GSlinas, I., & Gauthier, L. (1997) · International Psychogeriatrics · doi:10.1017/s1041610297004857 · Cited by 129 · see citing works
Follow-up of [ 11 C]PIB uptake and brain volume in patients with Alzheimer disease and controls
Scheinin, N. M., Aalto, S., Koikkalainen, J. R., Lötjönen, J. M. P., Karrasch, M., Kemppainen, N. M., Viitanen, M. H., Någren, K., Helin, S., Scheinin, M., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bacf1b · Cited by 128 · see citing works
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Villemagne, V. L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K. A., Salvado, O., Szoeke, C., Macaulay, S. L., Martins, R., Maruff, P., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70044-9 · Cited by 2,279 · see citing works
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188 · see citing works
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960 · see citing works
Self-citationBiomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002 · see citing works
The Preclinical Alzheimer Cognitive Composite: Measuring Amyloid-Related Decline
Donohue, M. C., Sperling, R. A., Salmon, D. P., Rentz, D. M., Raman, R., Thomas, R. G., Weiner, M., & Aisen, P. S. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.803 · Cited by 860 · see citing works
Brain Imaging in Alzheimer Disease
Johnson, K. A., Fox, N. C., Sperling, R. A., & Klunk, W. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006213 · Cited by 875 · see citing works
Self-citationLongitudinal assessment of Aβ and cognition in aging and Alzheimer disease
Villemagne, V. L., Pike, K. E., Chételat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22248 · Cited by 833 · see citing works
Self-citationThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Schneider, L. S., Mangialasche, F., Andreasen, N., Feldman, H., Giacobini, E., Jones, R., Mantua, V., Mecocci, P., Pani, L., Winblad, B., et al. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12191 · Cited by 651 · see citing works
Anti-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
Bateman, R. J., Aisen, P. S., De Strooper, B., Fox, N. C., Lemere, C. A., Ringman, J. M., Salloway, S., Sperling, R. A., Windisch, M., & Xiong, C. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt59 · Cited by 573 · see citing works
Self-citationTesting 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
Sperling, R., Salloway, S., Brooks, D. J., Tampieri, D., Barakos, J., Fox, N. C., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., et al. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70015-7 · Cited by 512 · see citing works
Self-citationReactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer’s Disease
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., & Hyman, B. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.05.047 · Cited by 488 · 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
Jucker, M. (2010) · Nature Medicine · doi:10.1038/nm.2224 · Cited by 401 · see citing works
Landau, S. M., Fero, A., Baker, S. L., Koeppe, R., Mintun, M., Chen, K., Reiman, E. M., & Jagust, W. J. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.114.148981 · Cited by 364 · see citing works
Amyloid‐β associated cortical thinning in clinically normal elderly
Becker, J. A., Hedden, T., Carmasin, J., Maye, J., Rentz, D. M., Putcha, D., Fischl, B., Greve, D. N., Marshall, G. A., Salloway, S., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22333 · Cited by 342 · see citing works
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease
Brothers, H. M., Gosztyla, M. L., & Robinson, S. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00118 · Cited by 314 · see citing works
Jeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101496 · Cited by 306 · see citing works
Bateman, R. J., Benzinger, T. L., Berry, S., Clifford, D. B., Duggan, C., Fagan, A. M., Fanning, K., Farlow, M. R., Hassenstab, J., McDade, E. M., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.07.005 · Cited by 303 · see citing works
Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials
Vandenberghe, R., Rinne, J. O., Boada, M., Katayama, S., Scheltens, P., Vellas, B., Tuchman, M., Gass, A., Fiebach, J. B., Hill, D., et al. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0189-7 · Cited by 304 · see citing works
Self-citationImmunotherapeutic 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
Villain, N., Chételat, G., Grassiot, B., Bourgeat, P., Jones, G., Ellis, K. A., Ames, D., Martins, R. N., Eustache, F., Salvado, O., et al. (2012) · Brain · doi:10.1093/brain/aws125 · Cited by 255 · see citing works
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Keren, R., Porsteinsson, A. P., van Dyck, C. H., Tariot, P. N., Gilman, S., Arnold, D., Abushakra, S., Hernandez, C., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e3182309fa5 · Cited by 258 · see citing works
Clinical amyloid imaging in Alzheimer's disease
Herholz, K., & Ebmeier, K. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70123-5 · Cited by 240 · see citing works
Zetterberg, H. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.90 · Cited by 234 · see citing works
Immunotherapy for Alzheimer’s disease: Key Symposium: Immunotherapy for Alzheimer’s disease
Morgan, D. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02315.x · Cited by 225 · see citing works
Drachman, D. A. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.11.003 · Cited by 224 · see citing works
Combination Drug Therapy for the Management of Alzheimer’s Disease
Kabir, M. T., Uddin, M. S., Mamun, A. A., Jeandet, P., Aleya, L., Mansouri, R. A., Ashraf, G. M., Mathew, B., Bin-Jumah, M. N., & Abdel-Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093272 · Cited by 217 · see citing works
Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
Lawlor, B., Segurado, R., Kennelly, S., Olde Rikkert, M. G. M., Howard, R., Pasquier, F., Börjesson-Hanson, A., Tsolaki, M., Lucca, U., Molloy, D. W., et al. (2018) · PLOS Medicine · doi:10.1371/journal.pmed.1002660 · 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
Goure, W. F., Krafft, G. A., Jerecic, J., & Hefti, F. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt272 · Cited by 190 · see citing works
Wolk, D. A. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.153 · Cited by 156 · see citing works
Alzheimer’s disease, cerebrovascular disease, and the β-amyloid cascade
Honjo, K., Black, S. E., & Verhoeff, N. P. L. G. (2012) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100015547 · Cited by 152 · see citing works
New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer's Disease
Fuller, J. P., Stavenhagen, J. B., & Teeling, J. L. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00235 · Cited by 154 · see citing works
Amyloid-β <sup>11</sup> C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials
Liu, E., Schmidt, M. E., Margolin, R., Sperling, R., Koeppe, R., Mason, N. S., Klunk, W. E., Mathis, C. A., Salloway, S., Fox, N. C., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001877 · Cited by 151 · see citing works
Self-citationVellas, B., Carrillo, M. C., Sampaio, C., Brashear, H. R., Siemers, E., Hampel, H., Schneider, L. S., Weiner, M., Doody, R., Khachaturian, Z., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.03.007 · Cited by 147 · see citing works
Self-citationMartins, R. N., Villemagne, V., Sohrabi, H. R., Chatterjee, P., Shah, T. M., Verdile, G., Fraser, P., Taddei, K., Gupta, V. B., Rainey-Smith, S. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171145 · Cited by 129 · see citing works
Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello, C., Yuan, P., & Grutzendler, J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.007 · Cited by 131 · see citing works
Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
Lee, V. M.-Y., Brunden, K. R., Hutton, M., & Trojanowski, J. Q. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006437 · Cited by 122 · see citing works
Mild to moderate Alzheimer dementia with insufficient neuropathological changes
Serrano‐Pozo, A., Qian, J., Monsell, S. E., Blacker, D., Gómez‐Isla, T., Betensky, R. A., Growdon, J. H., Johnson, K. A., Frosch, M. P., Sperling, R. A., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24125 · Cited by 120 · see citing works
Aβ-amyloid and Tau Imaging in Dementia
Villemagne, V. L., Doré, V., Bourgeat, P., Burnham, S. C., Laws, S., Salvado, O., Masters, C. L., & Rowe, C. C. (2017) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2016.09.006 · Cited by 110 · see citing works
Toward the Treatment and Prevention of Alzheimer's Disease: Rational Strategies and Recent Progress
Gandy, S., & DeKosky, S. T. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-092611-084441 · Cited by 110 · see citing works
Ferreira, L. K., & Busatto, G. F. (2011) · Clinics · doi:10.1590/s1807-59322011001300003 · Cited by 102 · see citing works
Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease
Vandenberghe, R., Adamczuk, K., Dupont, P., Laere, K. V., & Chételat, G. (2013) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.03.014 · Cited by 99 · see citing works
Weigand, S. D., Vemuri, P., Wiste, H. J., Senjem, M. L., Pankratz, V. S., Aisen, P. S., Weiner, M. W., Petersen, R. C., Shaw, L. M., Trojanowski, J. Q., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2010.08.230 · Cited by 93 · see citing works
Mahaman, Y. A. R., Huang, F., Wu, M., Wang, Y., Wei, Z., Bao, J., Salissou, M. T. M., Ke, D., Wang, Q., Liu, R., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180091 · Cited by 93 · see citing works
Drugs: A tangled web of targets
Gravitz, L. (2011) · Nature · doi:10.1038/475s9a · Cited by 81 · see citing works
Aβ immunotherapy for Alzheimer’s disease: effects on apoE and cerebral vasculopathy
Sakai, K., Boche, D., Carare, R., Johnston, D., Holmes, C., Love, S., & Nicoll, J. A. R. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1340-9 · Cited by 72 · see citing works
Modulation of γ- and β-secretases as early prevention against Alzheimer's disease
Voytyuk, I., De Strooper, B., & Chávez-Gutiérrez, L. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.001 · Cited by 67 · see citing works
Zhang, S., Smailagic, N., Hyde, C., Noel-Storr, A. H., Takwoingi, Y., McShane, R., & Feng, J. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010386.pub2 · Cited by 66 · see citing works
Schug, D., Nadig, V., Weissler, B., Gebhardt, P., & Schulz, V. (2019) · IEEE Transactions on Radiation and Plasma Medical Sciences · doi:10.1109/trpms.2018.2884564 · Cited by 56 · see citing works
Goñi, F., Herline, K., Peyser, D., Wong, K., Ji, Y., Sun, Y., Mehta, P., & Wisniewski, T. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-150 · Cited by 43 · see citing works
Qiao, Y., Gu, J., Yu, M., Chi, Y., & Ma, Y. (2024) · CNS Drugs · doi:10.1007/s40263-024-01067-2 · Cited by 38 · see citing works
Davtyan, H., Hovakimyan, A., Kiani Shabestari, S., Antonyan, T., Coburn, M. A., Zagorski, K., Chailyan, G., Petrushina, I., Svystun, O., Danhash, E., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0556-2 · Cited by 37 · see citing works
Pankiewicz, J. E., Baquero-Buitrago, J., Sanchez, S., Lopez-Contreras, J., Kim, J., Sullivan, P. M., Holtzman, D. M., & Sadowski, M. J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0156-1 · Cited by 34 · see citing works
Antibody Engineering for Optimized Immunotherapy in Alzheimer's Disease
Sumner, I. L., Edwards, R. A., Asuni, A. A., & Teeling, J. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00254 · Cited by 24 · see citing works
Alzheimer’s Disease: Dawn of a New Era?
Amirrad, F., Bousoik, E., Shamloo, K., Al-Shiyab, H., Nguyen, V.-H. V., & Montazeri Aliabadi, H. (2017) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j3vs8p · Cited by 21 · see citing works
“Phase II/III trials of gantenerumab were initiated in July 2010 and enrolled 799 patients (SCarlet RoAD NCT01224106) and was the first large trial to utilize new diagnostic criteria by the International Working Group to enroll a homogenous population of early symptomatic patients whose memory deficit was likely due to…”
MethodInfluential
- Authors
- Rinne, J. O., Brooks, D. J., Rossor, M. N., Fox, N. C., Bullock, R., Klunk, W. E., Mathis, C. A., Blennow, K., Barakos, J., Okello, A. A., de LIano, S. R. M., Liu, E., Koller, M., Gregg, K. M., Schenk, D., Black, R., & Grundman, M.
- Affiliations
- University of Turku (FI)
- Imperial College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- University of Pittsburgh Medical Center (US)
- Sahlgrenska University Hospital (SE)
- California Pacific Medical Center (US)
- Janssen Alzheimer Immunotherapy Research & Development (United States) (US)
- Elan Pharmaceuticals, Inc. (Ireland) (IE)
- Pfizer (United States) (US)
- Corresponding author
- Rinne, Juha O
- ORCID
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 9
- Issue
- 4
- Pages
- 363-372
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2150231759
- Cited by
- 701
- References
- 37
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 20 · 2022: 31 · 2021: 31 · 2020: 34 · 2019: 16 · 2018: 33 · 2017: 38 · 2016: 48 · 2015: 47 · 2014: 73 · 2013: 97 · 2012: 77
- FWCI
- 64.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0508-10123)
- 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
- bapineuzumab, Alzheimer's disease, amyloid-beta, 11C-PiB PET, anti-amyloid monoclonal antibodies, amyloid PET, treatment response assessment, dose escalation, mild to moderate Alzheimer's disease, anti-amyloid therapy
- MeSH terms
- Aged, Alzheimer Disease, Aniline Compounds, Antibodies, Monoclonal, Brain, Brain Mapping, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Immunologic Factors, Male, Severity of Illness Index, Thiazoles, Time Factors, Amyloid beta-Peptides, Treatment Outcome, Positron-Emission Tomography, Antibodies, Monoclonal, Humanized
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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.
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