Opinion: The trouble with mice as behavioral models for Alzheimer’s and other neurologic diseases

There’s been a lot of talk about overinvestment in interventions aimed at amyloid in the weeks since Biogen discontinued a late-stage study of aducanumab, an experimental therapy for Alzheimer’s disease.

Although much of the focus has been on the amyloid hypothesis at the heart of that work — and other failed treatments — I believe we are overlooking another key driver for numerous translational failures: the overreliance on behavioral readouts from contrived transgenic rodent models to guide drug development for Alzheimer’s, Parkinson’s, and other neurologic diseases. We need to find ways to move beyond this flawed paradigm.

The Food and Drug Administration has put in place well-established guidelines for preclinical safety studies. But the