This three-year, $5.782 million project grant from the National Institute on Aging, part of the Department of Health and Human Services, will support research into single-cell characterization of frontotemporal lobar degeneration caused by mutations in the progranulin gene. The University of California, San Francisco will map the transcriptome and gene regulatory networks that define glial pathology and neuronal vulnerability in the frontal cortex and thalamus of progranulin-deficient patients. Researchers will also characterize mechanisms of cellular resilience in neurons and glia in the visual cortex and delineate the functional consequences of transcriptomic and epigenetic changes using induced pluripotent stem cell models. This work aims to provide new insights into the trajectories of glial and neuronal pathology and region-specific vulnerability and resilience in this form of frontotemporal dementia. Results may yield biomarkers to predict disease progression. The research aligns with the goals of the National Institute on Aging's Aging Research program to further understanding of aging and age-related diseases.
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