Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest that cognitive decline is the result of a complex pathophysiology and that targeting amyloid-alone may not be sufficient to treat Alzheimer's disease. Instead, a broad outlook on neural-circuit-damaging processes may yield insights into new therapeutic strategies for curing memory loss in the disease.
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We thank the US National Institutes of Health for grants R01 NS051874, R01 NS078839, RF1 AG042978 and RF1 AG047661 in support of L.-H.T. We thank the Barbara J. Weedon Fellowship and Norman B. Leventhal Fellowship for supporting R.G.C. and the Human Frontier Science Program for supporting J.P. We also thank the JPB Foundation, the Belfer Neurodegeneration Consortium, the Glenn Foundation for Medical Research, the Cure Alzheimer's Fund and the Alana Foundation for support of L.-H.T. and for continued championship of ageing and neurodegenerative disease research. We thank C. Yao for contributions to the original figure artwork. Last, we express profound gratitude to A. Watson, H. Meharena, W. Raja and N. Dedic for insightful comments on the manuscript.
The authors declare no competing financial interests.
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Reviewer Information Nature thanks the anonymous reviewer(s) for their contribution to the peer review of this work.
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Canter, R., Penney, J. & Tsai, LH. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature 539, 187–196 (2016). https://doi.org/10.1038/nature20412
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