Complex diseases such as late-onset Alzheimer’s disease (LOAD) arise from the downstream interplay of DNA sequence variants and non-genetic factors that act through molecular networks to confer disease risk (Schadt, 2009). Despite decades of intensive research, the causal chain of mechanisms behind LOAD remains elusive. In fact, there are no effective disease modifying or preventive therapies and the only available treatment remains symptomatic; meanwhile the incidence of LOAD is expected to double by 2050 (Brookmeyer et al., 2007). Progress in LOAD research is fundamentally limited by our reliance on mouse models of severe familial/early-onset Alzheimer’s disease: therefore our primary knowledge of LOAD is in actuality based on the downstream effects of three rare mutations in APP, PSEN1 and PSEN2 (Bertram et al., 2010). While such mouse models are necessary and helpful, the cognitive deficits in these transgenic mice are less severe than those in humans and they do not exhibit equivalent neurodegeneration, which is the most accurate clinical marker of cognitive disease progression in humans. Correspondingly, attrition rates from early discovery to late drug development have been very high (Schafer and Kolkhof, 2008).
