The Dementia Imaging Genetics Laboratory is led by Dr. Suzee Lee, a behavioral neurologist and physician-scientist, at the University of California, San Francisco (UCSF) Memory and Aging Center.
Our mission is to understand the underlying biology of genetic dementias to improve the diagnosis and monitoring of preclinical and early-stage disease. Using quantitive structural MRI and task-free fMRI, we map the neural circuits targeted in genetic frontotemporal lobar degeneration (FTLD). One of the fundamental mysteries in genetic FTLD is why family members carrying the same mutation may manifest a variety of related diseases including behavioral variant frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, amyotrophic lateral sclerosis, and primary progressive aphasia. We believe that in studying genetic families, we may disentangle the complex network of genotype-phenotype relationships in order to determine which factors may influence age of onset and disease prognosis.
Because the vast majority of human disease is not caused by autosomal dominant genetic mutations, we are also interested in rare genetic risk and protective variants that may influence the development of dementia. Using next generation sequencing, we seek to identify novel genetic variants associated with dementia.
Our ultimate goal is to understand if and when disease starts before symptom onset and to develop brain imaging techniques for monitoring changes throughout the lifespan and in drug treatment trials.
Single-patient task-free functional MRI analyses of C9ORF72 hexanucleotide expansion carriers with mild symptoms or slow disease progression who show: A) normal structural MRI, B) connectivity reductions in the salience network, a network of regions important for detecting emotionally salient stimuli, C) connectivity reductions in the sensorimotor network, and D) enhancements and disruptions in the default mode network. Adapted from Lee et al. Brain 2014.