Different tau aggregate conformations and the rate of progression of tau Lead Investigator: Sarah Kaufman Institution : University of Texas Southwestern E-Mail : kaufmans@wusm.wustl.edu Proposal ID : 519 Proposal Description: We are currently investigating the role of distinct tau aggregate conformations on the pattern and rate of spread of tau pathology through the brain. We have observed that inoculation of different aggregate conformations into a mouse tauopathy model produces different rates of spread of tau pathology. This suggests that conformation may dictate the rate of spread of tau pathology, and may play a role in the rate of progression observed in different Alzheimer's disease patients. To begin to test whether this may occur in human patients, we must first identify subjects that demonstrating different rates of progression (fast/normal/slow). These patients would be identified based on their age of onset and CDR status at onset, their age and CDR status at their last clinical assessment, and their age and final pathological status upon autopsy. These patients would be stratified based on rate of progression, and relevant samples (2-3 per group) would be requested for assessment of the different tau aggregate conformations present in the tissue, and the rate of progression of tau pathology that these patient samples induce in a mouse tauopathy model.