Advancing the Alzheimer’s cause

Imagine you’re swimming in a familiar pool, but can’t find a way out of the water. The exit ladder was always in the same corner on your previous visits. This time, however, you can’t find it anywhere.
Now imagine the same scenario if, in addition, you had Alzheimer’s disease.
Known as the Morris water maze, this spatial memory test is one way researchers at Robarts are studying a gene associated with the disease’s pathology.
Robarts scientists Marco Prado, PhD and Vania Prado, DDS, PhD, along with their lab and collaborator Michael Jackson from The University of Manitoba, have shown that this particular gene, TRPM2, is responsible for coding a protein linked to toxicity in Alzheimer’s.
Their findings were published recently in the Journal of Neuroscience. Co-first authors on the paper were postdoctoral fellow Valeriy Ostapchenko, PhD, and former graduate trainee Megan Chen, MSc’13.
Using Alzheimer’s mouse models, one with the TRPM2 gene and one without, the Prado lab researchers introduced an escape platform in the water. Allowing a few days for memory training, the platform was eventually removed.
Those mice with the gene remained confused and disoriented in trying to find a way out of the water. But those without TRPM2 remembered the water maze’s escape route, spending a much longer time circling around where the missing platform used to be.
The test demonstrates that TRMP2 could be a potential therapeutic target to decrease cognitive dysfunction in Alzheimer’s.
“Without TRMP2 the typical plaques and aggregated proteins of Alzheimer’s still exist, but are less toxic,” explained Prado. “We found a missing element that normally interacts with Alzheimer’s pathology to increase toxicity.”
The work was the result of a prediction made five years ago by the late John Macdonald, former scientific director at Robarts. During his research into stroke and Alzheimer’s disease, the gene kept popping up and he engaged the Prado lab to help test its role and function.
This made the study’s conclusion a significant personal milestone. “All the co-authors are very proud that we were able to help John test this hypothesis,” Prado said. “The paper has an added emotional element because this is the last work he did.”
The scientist also sees the paper as an important step in the global effort to understand Alzheimer’s.
“Understanding the biology behind Alzheimer’s disease is essential,” said Prado. “We still don’t really understand how this disease develops. If we have a clearer picture, we can figure out what are the best drug targets and how we can intervene early on.”