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Failure analysis of clinical trials to test the amyloid hypothesis

2014; Wiley; Volume: 76; Issue: 2 Linguagem: Inglês

10.1002/ana.24227

1531-8249

Bradley T. Hyman, Peter K. Sorger,

Cholinesterase and Neurodegenerative Diseases

Annals of NeurologyVolume 76, Issue 2 p. 159-161 Commentary Failure analysis of clinical trials to test the amyloid hypothesis Bradley T. Hyman MD, PhD, Bradley T. Hyman MD, PhD Neurology Service, Massachusetts General Hospital, Boston, MASearch for more papers by this authorPeter Sorger PhD, Peter Sorger PhD Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MASearch for more papers by this author Bradley T. Hyman MD, PhD, Bradley T. Hyman MD, PhD Neurology Service, Massachusetts General Hospital, Boston, MASearch for more papers by this authorPeter Sorger PhD, Peter Sorger PhD Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MASearch for more papers by this author First published: 15 July 2014 https://doi.org/10.1002/ana.24227Citations: 12Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353–356. 2 Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: a006312. 3 Jonsson T, Atwal JK, Steinberg S, et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012; 488: 96–99. 4 Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 2011; 10: 698–712. 5 Oyama F, Cairns NJ, Shimada H, et al. Down's syndrome: up-regulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination. J Neurochem 1994; 62: 1062–1066. 6 Rovelet-Lecrux A, Hannequin D, Raux G, et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 2006; 38: 24–26. 7 Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2(10). 8 Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 2012; 71: 362–381. 9 Serrano-Pozo A, Qian J, Monsell SE, et al. Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center. J Neuropathol Exp Neurol 2013; 72: 1182–1192. 10 Karran E, Hardy J. A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann Neurol 2014; 76: 185–205. 11 Toyn JH, Ahlijanian M. Interpreting Alzheimer's disease clinical trials in light of the effects on amyloid-β. Alzheimer Res Ther 2014; 6: 14. 12 Hyman BT. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol 2011; 68: 1062–1064. 13 Serrano-Pozo A, Qian J, Monsell SE, et al. Mild to moderate Alzheimer dementia with insufficient neuropathological changes. Ann Neurol 2014; 75: 597–601. 14 Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 2012; 367: 795–804. 15 Mullard A. Sting of Alzheimer's failures offset by upcoming prevention trials. Nat Rev Drug Discov 2012; 11: 657–660. Citing Literature Volume76, Issue2August 2014Pages 159-161 ReferencesRelatedInformation