It’s time to move away from mouse models of Alzheimer’s Disease

The inadequacy of mice and other animals to serve as stand-ins for humans is no secret. This inadequacy—and the subsequent need to develop human-relevant alternatives—drives NAVS’ investment in early career researchers through the International Foundation for Ethical Research (IFER).

The failure of mouse models is now being recognized among researchers striving to find a cure for Alzheimer’s disease, the sixth leading cause of death in the United States. Alzheimer’s is the most common form of dementia, affecting memory, thinking and behavior. According to the Alzheimer’s Association, approximately 5.7 million Americans currently suffer from Alzheimer’s disease, and numbers are expected to grow.

Billions of dollars and decades of research dedicated to Alzheimer’s disease have failed to produce a successful treatment, and many researchers have attributed this failure to heavy reliance on mouse models of the disease. Many of these models were mice that were genetically modified to express genes associated with Alzheimer’s disease but failed to mimic many of the key aspects of the human condition.

According to Dr. Bruce Lamb, neuroscientist at Indiana University, “We appreciate that the models we had were insufficient.  I think it’s sort of at a critical juncture now.”

While recognition of these limitations has led some researchers to devote their resources into the development of more human-relevant models of Alzheimer’s disease, including researchers that NAVS funds through IFER, others in the scientific community are opting to develop even more animal models of the condition.

According to a recent Nature article, some researchers in the Alzheimer’s field are interested in moving away from inbred lab mice and believe that using mice with more genetic diversity would strengthen the animal models of the disease. There is also a consortium initiated by the National Institutes of Health to make more Alzheimer’s mouse models as research tools for the scientific community by focusing on genetic mutations implicated in both the early- and late-onset forms of the disease. About thirty such mouse varieties have been developed through this initiative.

Given the historical failure of mouse models of Alzheimer’s disease, it is disappointing to see more time and taxpayer money being used to fund these initiatives. Mouse models of Alzheimer’s disease do not work. As Dr. Bart de Strooper of the Catholic University of Leuven in Belgium stated, “The biggest mistake you can make is to think you can ever have a mouse with Alzheimer’s disease.”

The time and money that are being invested in Alzheimer’s research should be directed toward more human-relevant research. Advances in stem cell technologies have given researchers the ability to derive neurons from human induced pluripotent stems cells from patients with Alzheimer’s and individuals without dementia, which serve as useful and human-relevant models for disease modeling and preclinical drug discovery and development.

Use of these models has already provided valuable insight into the biological changes that take place within neurons in individuals with Alzheimer’s to help explain how the disease develops and progresses. These approaches offer many advantages over animal models used to study the disease—including human-relevance and improved recapitulation of disease pathology—while producing results more quickly, cheaply and humanely than animal models.  

Science First will not be published on December 24th and 31st. We will return on Monday, January 7th, 2019. Happy Holidays!

Source: Reardon, S. “Alzheimer’s researchers seek better mice,” Nature, November 29, 2018.

This entry was posted in News and tagged on December 18, 2018.
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