Relationship Between Age and Resilience to Alzheimer's and Susceptibility to
non-Alzheimer Pathologies 
   Lead Investigator:    Kiana Scambray
   Institution      :    University of California, Irvine
   E-Mail           :    kscambra@uci.edu
   Proposal ID      :    1363



   Proposal Description:
   Recent developments in dementia research have unveiled the impact multiple pathologies have on cognition. While pathological hallmarks of Alzheimer's disease namely, amyloid beta (A#946) plaques and neurofibrillary tangles largely contribute to cognitive decline, multiple studies have demonstrated the need to look further into other pathologies such as TDP-43 and alpha synuclein to develop a more cohesive understanding of the degenerative brain diseases and how they associate to the clinical manifestation of dementia.                      In the proposed project, our goal is to better understand how different pathologies contribute to cognitive decline at different stages of late adult life.  We hypothesize that younger elderly are more susceptible to the aggregation of A#946 plaques and neurofibrillary tangles compared to older elderly who seem to acquire some resilience to aggregation of  AD pathology markers. We further hypothesize that the older elderly become vulnerable to other pathologies such as TDP-43, resulting in their cognitive decline.     Through this project, we aim to explore the notion that other pathologies such as TDP-43 may play a larger role in contributing to cognitive decline after individuals reach an older age. In gaining a better understanding of the relationship between pathology and age, new therapeutic interventions can be explored to better target the source of decline in cognition.