Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift.
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.
Center for Translational Research in Neurodegenerative Disease and Department of Neuroscience, College of Medicine, University of Florida, 1275 Center Drive BMS J-483, P.O. Box 100159, Gainesville, FL 32610-0244, USA. tgolde@mbi.ufl.edu
Todd E
TE
Golde
Lon S
LS
Schneider
Edward H
EH
Koo
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006301:Health Services Needs and Demand; D006801:Humans; D057170:Translational Research, Biomedical
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers
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