Evaluating genetic risk factors of hippocampal sclerosis (HS) in FTLD

 
   Lead Investigator:    Pete Nelson
   Institution      :    U Kentucky
   E-Mail           :    pnels2@uky.edu
   Proposal ID      :    423


   Publications:


1  Nelson PT, Trojanowski JQ, Abner EL, Al-Janabi OM, Jicha GA, Schmitt FA, Smith CD, Fardo DW, Wang WX, Kryscio RJ, Neltner JH,  Kukull WA,  Cykowski MD, Van Eldik LJ, Ighodaro ET
   New Old Pathologies: AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS)
   Journal Article  J Neuropathol Exp Neurol,75:482-98,2016,PMC6366658

   PUBLISHED



2  Nelson PT, Wang WX, Partch AB,  Monsell S , Valladares O, Ellingson SR, Wilfred BR, Naj AC, Wang LS,  Kukull WA , Fardo DW
   Reassessment of risk genotypes (GRN, TMEM106B, and ABCC9 variants) associated with hippocampal sclerosis of aging pathology
   Journal Article  J Neuropathol Exp Neurol,74:75-84,2015,PMC4270894

   PUBLISHED





   Proposal Description:
   We recently found that polymorphism in ABCC9 is a genetic risk factor for hippocampal sclerosis of aging (HS-Aging).  HS-Aging is a disease that is characterized by hippocampal atrophy and, frequently, TDP-43 pathology.  Another subtype of brain disease with dementia and hippocampal TDP-43 pathology is frontotemporal lobar degeneration, FTLD.  (FTLD also frequently co-occurs with HS, although this seems to have some aspects different from HS-Aging).  A natural question relates to whether ABCC9 is also a risk factor for HS that is seen in FTLD cases.  To address this question, we are requesting data from NACC database which can then be correlated to the ADGC database.  We previously probed the NACC dataset and used data where FTLD cases were excluded.  We now are requesting the opposite: a dataset with FTLD cases, to perform genomic study of ABCC9 and to probe possible interactions with other loci already shown to be FTLD risk factors (GRN and TMEM106B).