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Two decades testing interventions in transgenic mouse models of Alzheimers disease: designing and interpreting studies for clinical trial success

Kieren Egan, & Malcolm Macleod

The increasing prevalence of Alzheimer’s disease (AD) poses considerable socioeconomic challenges. Decades of experimental research are yet to lead to the development of effective disease-modifying interventions. The limitations of in vivo research in AD are currently poorly understood and a deeper understanding of these might assist future research and trial design. Here we use examples from translational research in AD and across the neurosciences to illustrate how we might increase experimental rigour and thereby raise the validity of studies. We show that there are considerable weaknesses in the in vivo modeling of AD, and therefore clinical trials based on claims of efficacy in animals should proceed only after it has been shown that those claims are well founded.