Identification of endophenotypes in frontotemporal degeneration

 
   Lead Investigator:    David Irwin
   Institution      :    University of Pennsylvania
   E-Mail           :    dirwin@mail.med.upenn.edu
   Proposal ID      :    647


   Publications:


1  Irwin DJ, Grossman M, Weintraub D, Hurtig HI, Duda JE, Xie SX, Lee EB, Van Deerlin VM, Lopez OL, Kofler JK, Nelson PT, Jicha GA, Woltjer R, Quinn JF, Kaye J, Leverenz JB, Tsuang D, Longfellow K, Yearout D,  Kukull WA , Keene CD, Montine TJ, Zabetian CP, Trojanowski JQ.
   Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis
   Journal Article  Lancet Neurol,1:55-56,2017,PMC5181646

   PUBLISHED



2  Phillips JS, Irwin DJ, Rascovsky K, Van Deerlin VM, Lee VM, Trojanowski JQ, McMillan CT, Grossman M
   Cognitive and Behavioral Trajectory of Behavioral-Variant Frontotemporal Dementia Differs According to Underlying Pathology
   Abstract  J Neurochem,138:297-298,2016,

   PUBLISHED





   Proposal Description:
   A major limitation of the diagnosis of frontotemporal degeneration (FTLD) is the inability of clinical phenotypes (e.g. behavioral-variant frontotemporal dementia bvFTD, corticobasal syndrome CBS, primary progressive aphasia PPA) to accurately predict underlying neuropathology. This is a critical obstacle to the development and implementation of disease modifying therapies which target the protein constituents of the two major subtypes of this condition (i.e. FTLD-Tau and FTLD-TDP). Aim#1: Identification of endophenotypes of FTLD. I hypothesize that patterns of disease progression differ in FTLD-Tau and FTLD-TDP and these divergent pathways are clinically detectable. ??I propose to examine detailed clinical records of cases with autopsy or genetic confirmation of FTLD neuropathology, together with clinical phenotypes highly predictive of pathology (ALS-FTD, PSP) at the PENN and NACC cohort to identify features predictive in differentiate FTLD-Tau and FTLD-TDP (i.e. endophenotypes) using a discovery (PENN) and test (NACC) set approach. I will relate these clinical measures to regional distribution of pathology on histology and neuroimaging in the PENN cohort.??