Can We Prevent Dementia and Not Prevent Neurons from Dying?

Journal of Alzheimer's Disease : JAD
Robert E Becker, Nigel H Greig

Abstract

Neuronal death is the final step in the progression of preclinical Alzheimer's disease (AD) pathologies into clinically evident AD and its profound dementia. As such, a drug candidate proposed to be effective in AD must successfully prevent neuronal losses. The lack of preclinical demonstrated abilities to prevent neuronal programmed cell death may explain the recent failure of 300-400 AD drug candidates, identify a flaw in the Amyloid Hypothesis, and a risk for subsequent drug candidate interventions against AD. We propose that investigators use either animal models or small early translational clinical trials to test for AD drug candidates' efficacy against clinically critical features of the disease, such as prevention of neuronal death. Such stringent testing would more effectively shelter AD patients from being recruited into clinical trials that are destined to fail in Phase II or III.

References

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Oct 28, 2008·Journal of Alzheimer's Disease : JAD·Robert E BeckerEzio Giacobini
Dec 17, 2009·Brain Structure & Function·Thomas Wisniewski, Allal Boutajangout
Jun 28, 2011·Nature Reviews. Drug Discovery·David C Swinney, Jason Anthony
Dec 24, 2013·Nature Reviews. Drug Discovery·Robert E BeckerLuigi Ferrucci
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Mar 17, 2017·Science Translational Medicine·Gaia Novarino
Jun 8, 2017·Frontiers in Neuroscience·Maja MustapicDimitrios Kapogiannis
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Oct 1, 2017·Brain Research·Cheng-Fu ChangKai-Yun Chen
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Nov 28, 2018·Nature·Guoliang Chai, Joseph G Gleeson
Apr 26, 2018·Journal of Patient-centered Research and Reviews·Robert E Becker, Mary V Seeman

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Citations

Aug 14, 2019·Trends in Pharmacological Sciences·Miao-Kun Sun, Daniel L Alkon

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