Amyloid-β (Aβ) is suggested to have a pivotal role in the pathogenesis of Alzheimer disease (AD) and is a major therapeutic target. Recent phase III trials of the anti-Aβ monoclonal antibodies bapineuzumab and solanezumab, which failed to improve cognitive function in patients, provide valuable insights for the future development of immunotherapies.
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References
Salloway, S. et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 370, 322–333 (2014).
Doody, R. S. et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 370, 311–321 (2014).
Demattos, R. B. et al. A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer's disease mice. Neuron 76, 908–920 (2012).
Yamada, K. et al. Aβ immunotherapy: intracerebral sequestration of Aβ by an anti-Aβ monoclonal antibody 266 with high affinity to soluble Aβ. J. Neurosci. 29, 11393–11398 (2009).
Gardberg, A. S. et al. Molecular basis for passive immunotherapy of Alzheimer's disease. Proc. Natl Acad. Sci. USA 104, 15659–15664 (2007).
Zago, W. et al. Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: implications for amyloid-related imaging abnormalities. Alzheimers Dement. 9, S105–S115 (2013).
Liu, Y. H., Giunta, B., Zhou, H. D., Tan, J. & Wang, Y. J. Immunotherapy for Alzheimer disease: the challenge of adverse effects. Nat. Rev. Neurol. 8, 465–469 (2012).
Sehgal, N. et al. Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc. Natl Acad. Sci. USA 109, 3510–3515 (2012).
Henderson, S. J. et al. Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β. Brain 137, 553–564 (2013).
Krstic, D. & Knuesel, I. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev. Neurol. 9, 25–34 (2012).
Acknowledgements
Y.-J.W. is supported by the National Natural Science Foundation of China (grant numbers 81270423 and 30973144) and the Natural Science Foundation Project of Chongqing Science and Technology Committee (grant number CSTC2010BA5004). Y.-J.W. thanks Professors Jun Tan and Brian Giunta at the University of South Florida, USA for critical reading of the paper.
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Wang, YJ. Lessons from immunotherapy for Alzheimer disease. Nat Rev Neurol 10, 188–189 (2014). https://doi.org/10.1038/nrneurol.2014.44
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DOI: https://doi.org/10.1038/nrneurol.2014.44
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