Clearance of pathogenic amyloid-β (Aβ) deposits from patient brains is being investigated as a treatment approach for Alzheimer disease (AD). However, Phase III trial results of Aβ-targeting monoclonal antibodies have been disappointing. Using AD transgenic mice, Busche et al. reveal that although Aβ-targeting antibodies reduce amyloid pathology, they unexpectedly aggravate neuronal dysfunction, increase numbers of pathologically hyperactive neurons and promote abnormal synchrony of cortical activity.
References
Busche, M. A. et al. Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer's models. Nat. Neurosci. 18, 1725–1728 (2015)
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Crunkhorn, S. Aβ-targeting antibodies aggravate neuronal dysfunction. Nat Rev Drug Discov 15, 18 (2016). https://doi.org/10.1038/nrd.2015.29
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DOI: https://doi.org/10.1038/nrd.2015.29
