As its name suggests, Frontotemporal Dementia (FTD) is associated with progressive damage to the frontal and/or temporal lobes of the brain. Two important factors distinguish FTD from the more familiar type of dementia associated with Alzheimer’s disease (AD). First, patients with FTD experience progressive decline and disruption in cognitive domains including executive function, personality, or language, often with relative preservation of memory. This means that in the early stages of the disease some FTD patients may be misdiagnosed as suffering from psychiatric disorders. Second, FTD occurs at a much younger age than AD, affecting patients in their 50s and 60s and making FTD the leading cause of dementia in those younger than 65. There are currently no treatments to slow or stop the progression of FTD and no diagnostic tests to predict its onset or measure its progression.
This project, led by our team in collaboration with colleagues at the UCSF Memory and Aging Center and 15 other university medical departments and research centers from around the world, has uncovered genetic signals shared between patients with FTD and those with a variety of immune-mediated disorders. This genetic overlap is concentrated within the HLA region on Chromosome 6, an area rich in genes important for the function of microglia – the brain’s resident immune cells. Importantly, the shared FTD-immune genes that we identified are differentially expressed in the brains of FTD patients compared with controls, and in microglia compared with other CNS cells.
Our results suggest that for a subset of FTD patients immune dysfunction may contribute to disease risk and that future clinical trials should target immune dysfunction in patients with FTD. We are now investigating novel molecular imaging markers to image microglial activation in patients at risk for FTD.
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