Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift - PubMed (original) (raw)

Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift

Todd E Golde et al. Neuron. 2011.

Abstract

Most current Alzheimer's disease (AD) therapies in advanced phases of development target amyloid β-peptide (Aβ) production, aggregation, or accumulation. Translational models suggest that anti-Aβ therapies may be highly effective if tested as agents to prevent or delay development of the disease or as therapies for asymptomatic patients with very early signs of AD pathology. However, anti-Aβ therapeutics are currently being tested in symptomatic patients where they are likely to be much less effective or ineffective. The lack of alignment between human clinical studies and preclinical studies, together with predictions about optimal trial design based on our understanding of the initiating role of Aβ aggregates in AD, has created a treatment versus prevention dilemma. In this perspective, we discuss why it is imperative to resolve this dilemma and suggest ways for moving forward in the hopes of enhancing the development of truly effective AD therapeutics.

© 2011 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Preclinical AD

The newly proposed staging of preclinical or prodromal AD reflects a cascade beginning with Aβ accumulation in the brain of clinically asymptomatic individuals and inexorably progressing to AD.

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