UF neuroscience students lead creation of new mouse model for Alzheimer’s research

A research team led by University of Florida neuroscience graduate students has devised a new mouse model to study the protein tau, which can abnormally accumulate inside neurons and is associated with Alzheimer’s disease and related dementias. The development was reported May 12 in Communications Biology, a Nature Portfolio journal.

The new rodent model, which was engineered with a goal of gaining understanding into the interplay between peripheral and central nervous system tau pathology, is the first of its kind to result in the demise of gut neurons, the researchers reported. “As a model used for rapid drug screening, it will be advantageous to test the effects of lead compounds on the effects of pathogenic tau in both the gut and brain,” they wrote.

The new model expresses low levels of pathogenic human tau and is engineered to develop predictable progression of tau pathology with similarities to authentic tau brain changes, the authors said. The researchers dubbed the model “SPAM,” derived from the first letters of “S320F” and “P301S” (tau mutations), “aggregating” and “mutations.”

The project was led by M.D.-Ph.D. students Yuxing Xia, Lith Nasif and Stephan Quintin; Kevin Strang, Ph.D., a former graduate assistant; and doctoral student Giavanna Paterno under the guidance of Benoit Giasson, Ph.D., a professor of neuroscience, and in collaboration with Malú Gámez Tansey, Ph.D., whose expertise in the gut-brain axis was key for the studies.

“We hope this new tau model will help accelerate insights into disease mechanisms and future therapeutic discoveries for Alzheimer’s disease and some forms of frontotemporal dementias,” Giasson said.

Tansey, the Norman and Susan Fixel Professor of Neuroscience and Neurology and co-director of the Center for Translational Research in Neurodegenerative Disease, said the SPAM model will open the door to new lines of research into the contribution of immune cells that are outside the brain — in the gut and blood.

“Having an in vivo model like the SPAM mice where the contribution of immune cells in the gut and blood can be assessed to determine how the immune system protects against or predisposes an organism to development of neurodegeneration triggered by abnormal tau aggregation as a function of age, in response to chronic infection or chronic inflammation resulting from diet or lifestyle choices will enable translational neuroimmunological studies that will advance the field of neurodegeneration as a whole,” said Tansey.

By Michelle Jaffee, University of Florida