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Resolving controversies on the path to Alzheimer's therapeutics

Nature Medicine volume 17, pages 1060–1065 (2011)Cite this article

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A Corrigendum to this article was published on 06 December 2011

A Corrigendum to this article was published on 07 November 2011

This article has been updated

Abstract

Alzheimer's disease constitutes a personal and societal tragedy of immense proportions. Since 1960, research in laboratories and clinics worldwide has elucidated many features of this insidious and ultimately fatal syndrome, and this progress has led to initial human trials of potentially disease-modifying agents. However, some of these agents have already failed. Gnawing controversies and important gaps in our knowledge seem to cast additional doubt on the ability of the field to move forward effectively. Here I discuss some of these looming concerns and offer possible explanations for the major trial failures that suggest they are not predictive of the future. Rigorous preclinical validation of mechanism-based therapeutic agents followed by meticulously designed trials that focus on the cardinal cognitive symptoms and their associated biomarkers in the mild or presymptomatic phases of Alzheimer's disease are likely to lead to success, perhaps in the not-too-distant future.

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Figure 1: Approximate timeline of some principal discoveries in Alzheimer's disease research since 1960.
Figure 2: Intersecting disease-modifying agents for Alzheimer's disease with the course of the disease.

Change history

  • 21 October 2011

     In the version of this article initially published, the name of the antibody bapineuzumab is incorrectly spelled as 'bapineuzimab' throughout the text. The error has been corrected in the HTML and PDF versions of the article.

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Authors and Affiliations

  1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Dennis J Selkoe

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Competing interests

D.J.S. is a founding scientist of Athena Neurosciences and a consultant to Elan plc. He is also a consultant to Johnson & Johnson in neuroscience.

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Selkoe, D. Resolving controversies on the path to Alzheimer's therapeutics. Nat Med 17, 1060–1065 (2011). https://doi.org/10.1038/nm.2460

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