Researchers have engineered an improved model of Alzheimer’s disease. The new mouse has a greater degree of molecular and genetic overlap with the disorder than previous models, according to new work by scientists funded by the National Institute on Aging (NIA), a part of the National Institutes of Health (NIH). The shared features suggest that the changes, which added diversity to the genome of the mouse, were important for mimicking the disease. The research has been reported in Neuron.
“This is the first study to show that you can replicate many of the molecular features of Alzheimer’s disease in a genetically diverse mouse model,” noted NIA Director Richard J. Hodes, M.D. “It points to a strategy for better use of mouse models for precision medicine research -- both basic and translational -- for Alzheimer’s disease.”
It’s estimated that 5.5 million Americans older than 65 are impacted by Alzheimer’s. The degenerative disease damages and eventually destroys an affected individual’s memory and mind. It is the most common type of dementia.
Because it affects the brain, it presents a particular challenge for those studying the disease and makes a good mouse model a vital part of research efforts. The animals can help reveal the genes, proteins, and mechanisms that underlie the disorder. They also enable investigators to test potential therapeutics.
In this work, the research team wanted to add genetic diversity like what’s seen in nature to a mouse Alzheimer’s model. They aimed to develop an animal that parallels the complex characteristics of the disease more closely. They did so by mating a well-established Alzheimer’s mouse model with a diverse group of new mice.
The progeny of those matings carried genetic features like those found in Alzheimer’s but were otherwise highly diverse from a genetic standpoint. After a detailed assessment, the scientists found that their new mice had a high degree of similarity to Alzheimer’s when it came to genes, molecules, pathology, and cognition. The variation in other parts of their genomes also produced mice with a huge range of disease severity and age of onset of symptoms. One mouse was also protected from the disease.
It turned out to be one of the common strains of laboratory mice, the C57BL/6J, which harbored genetic variations that reduced the severity of Alzheimer’s. This mouse is often used in Alzheimer’s disease research work, suggesting that this model may not be ideal for studying the disorder or therapies. The protective genes may also reveal new drug targets for the prevention or treatment of Alzheimer’s.
“The ability to model genetic diversity and its impact on multiple aspects of disease risk and resilience in transgenic mice in a robust and reproducible way will enable the research community to learn a lot more about the complex nature of Alzheimer’s a lot faster,” said Suzana Petanceska, Ph.D., program director in the NIA Division of Neuroscience. “This new resource adds to the series of new NIA/NIH programs generating data, analytical and research tools needed to enable more efficient and predictive drug development for Alzheimer’s.”
