As she opened her talk, Dr. Simonyi discussed the various animal models that are used to study Alzheimer’s. Especially with this type of disease, it’s important to consider the different capabilities of a potential animal model. For instance, can the animal display both behavioral and physiological characteristics that are similar to those of humans with the disease in question?
Dr. Simonyi studies the TgCRND8 mouse model of Alzheimer’s and is currently studying its behavioral characteristics. These mice are genetically modified to express the human gene, APP. This gene plays a role in the development of amyloid plaques (or aggregated proteins), which are a prominent feature of Alzheimer’s disease.
With several behavioral tests, Dr. Simonyi is studying mouse behavioral traits that are similar to human symptoms of Alzheimer’s disease: disrupted physical activity, anxiety, memory impairments, and difficulties with activities of daily living (or self-help skills). I found how Dr. Simonyi is assessing activities of daily living to be particularly interesting.
For mice, a common “activity of daily living” would be building nests out of various materials. To assess this activity in an experimental setting, TgCRND8 mice and wild type (or normal) mice are given a square of bedding material in their home cage. About 24 hours later, the quality of a nest built out of the material is rated alongside a measure of how much of the material is torn up. Preliminary results indicate that the TgCRND8 mice are impaired in this nest-building activity, as compared to wild type mice. What’s interesting is how these behavioral deficits are present even before amyloid plaques can be detected in the brains of these mice.
Why is this important? In humans, the onset of behavioral symptoms of Alzheimer’s can trail the development of brain damage by as much as 30 years. As my advisor puts it: once you start to see behavioral symptoms of Alzheimer’s, the cat’s already out of the bag. If signs of memory impairment and other Alzheimer’s symptoms manifest only after a significant progression of the disease, it may be difficult to provide adequate treatment.
What Dr. Simonyi may be on to is an animal model that shows behavioral impairments before it’s too late. If we can learn more about how Alzheimer’s develops before irreversible changes in the brain occur, maybe we can find a way to keep the cat in the bag.
[This post was originally published at my previous blog, Neurolore.]