Thus, we cannot truly evaluate the potential of anti-Aβ or neuroprotection therapies to halt neuronal loss because there is such limited neuronal loss in current APP mouse models. Nevertheless, we can at least attempt to be more rigorous and self-critical

selleck screening library with respect to the potential clinical translation of preclinical data. There are many nonscientific and nonmedical challenges to implementing primary prevention or early intervention in AD. Some of the most challenging aspects are financial in nature; others are regulatory barriers. Phase 2 and 3 clinical trials in the pharmaceutical industry overall are inherently complicated, resource-intensive endeavors with high probabilities for failure. Together, phase 2 and 3 programs consume 48% of the costs for each drug launched and may cost on average $185 million and $235 million, respectively (Paul et al., 2010). Commercially sponsored AD therapeutic programs and most prevention trials are typically more expensive. It is difficult to source the costs of an AD prevention trial for industry as only one such trial has been sponsored: a Ginkgo biloba extract study in France involving about 2800 patients over

5 years (Vellas et al., 2006b). The National Institutes of Health has funded several prevention trials including Women’s Health Initiative-Memory Study (WHIMS), the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT), Ginkgo Evaluation of Memory Study (GEM) and PreAdvise (Craig et al., 2005, Kryscio et al., 2004, Martin et al., 2002 and Snitz et al., 2009). These trials were designed in a manner Autophagy Compound Library screening that cost significantly less than current industry-funded

treatment trials (Table 1). For example, some of the studies enhanced the likelihood for AD by choosing participants who were at higher risk or who isothipendyl already had MCI, outcomes were onset of AD or MCI, they had relatively short follow up periods of 4 to 7 years, and they did not incorporate the comprehensive biomarker or imaging assessments that are available today. This enabled recruitment of 2500 to 4500 participants. Based on publicly listed sources (http://www.projectreporter.nih.gov/reporter.cfm), the comparably large ADAPT (Lyketsos et al., 2007) and GEM Ginkgo biloba extract study (DeKosky et al., 2008) studies have respectively received approximately $44 million and $28 million of total funding. Total costs for these studies are likely higher as they typically leverage infrastructure within the National Institutes of Health and participating academic institutions. Taken together, it is reasonable to estimate that a federally-sponsored prevention trial would cost around U.S. $80–100 million for a 5 year U.S. study. Given this fiscal reality, we must explore ways to run well-powered primary prevention or early intervention studies that do not cost substantially more or even cost less.