Title | Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Golde, TE, Schneider, LS, Koo, EH |
Journal | Neuron |
Volume | 69 |
Issue | 2 |
Pagination | 203-13 |
Date Published | 2011 Jan 27 |
ISSN | 1097-4199 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Clinical Trials as Topic, Disease Progression, Health Services Needs and Demand, Humans, Translational Medical Research |
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. |
DOI | 10.1016/j.neuron.2011.01.002 |
Alternate Journal | Neuron |
PubMed ID | 21262461 |
PubMed Central ID | PMC3058906 |
Grant List | AG020206 / AG / NIA NIH HHS / United States AG05142 / AG / NIA NIH HHS / United States P01 AG020206 / AG / NIA NIH HHS / United States P01 AG020206-08 / AG / NIA NIH HHS / United States R01 AG018454 / AG / NIA NIH HHS / United States R01 AG018454-10 / AG / NIA NIH HHS / United States |