UF neuroscientist to co-lead study into causes of frontotemporal dementia

By Todd Taylor

Researchers from the University of Florida and two partner institutions will team up to explore possible links between the immune system and neurodegeneration in frontotemporal dementia under a new NIH/National Institute of Neurological Disorders and Stroke grant designed to support multi-disciplinary collaborations between neuroscientists, neurologists and immunologists.

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Dr. Malú Gámez Tansey

The five-year project will be funded in phases, with the first three years of the award totaling $2.45 million.

Frontotemporal dementia, or FTD, is the most common form of dementia in people younger than 60. An estimated 60% of people with FTD are between the ages of 45 and 64.

The research team will use novel human-cell models and mouse models to examine the crosstalk between peripheral immune cells and dysfunctional microglia and its effects on neuronal function and FTD-like pathology. The models include: mouse models of FTD with a mutation in the progranulin gene (GRN), a common cause of the disorder; human peripheral blood mononuclear cell models; and induced pluripotent stem cells, a type of pluripotent cells that can be obtained by reprogramming animal and human differentiated cells.

The research team is led by co-principal investigators Malú Gámez Tansey, Ph.D., co-director of UF’s Center for Translational Research in Neurodegenerative Disease, and Steve Finkbeiner, M.D., Ph.D., director of the Center for Systems and Therapeutics at UCSF and a senior investigator at The Gladstone Institute, and co-investigator Jessica Rexach, M.D., Ph.D., an assistant professor-in-residence of neurology at UCLA.

“We’ve assembled a fantastic team with complementary strengths and innovative approaches to test a novel hypothesis about how progranulin regulates both central and peripheral inflammation and immunity to affect brain function and neuronal survival,” said Tansey, the Norman and Susan Fixel Professor of Neuroscience and Neurology.

“We are going beyond mere comparison of transcriptionally defined disease-associated cellular signatures across models and linking these to functional readouts,” she said. “We will link correlation analyses between gene and protein expression trajectories in three model systems with experimentally-defined functional and phenotypic neuroimmune outcomes.”