Shape Analysis of Hippocampi between APOE e2 Carriers and Non-Carriers

 
   Lead Investigator:    Judy Pa
   Institution      :    Institute for Neuroimaging and Informatics, USC
   E-Mail           :    jpa@ini.usc.edu
   Proposal ID      :    525


   Publications:


1  Hobel Z, Isenberg A, Raghupathy D, Mack W, Pa J
   APOE ^{unicode 03b5}4 Gene Dose and Sex Effects on Alzheimer's Disease MRI Biomarkers in Older Adults with Mild Cognitive Impairment
   Journal Article  J Alzheimers Dis,71:647-658,2019,PMC6839478

   PUBLISHED





   Proposal Description:
   Our study will be investigating the shape differences of the left and right hippocampus among subjects with and without the e2 variant of the APOE gene.  Although e2 has been shown to protect against developing Alzheimer's disease (AD) and hippocampus shrinkage is correlated with the progression of AD, how the presence of e2 affects the shape of the hippocampus in aged populations has not been fully explored.  We also will study race-related differences amongst these groups.    Sub-aim (Stradford et al.)  Dr. Judy Pa's Gender Imaging Genetics (GIG) Project is funded NIH R01 with three aims. The first aim is to analyze brain deformation and cognitive decline. We hypothesize that hippocampal morphometry will be different between men and women based on APOE4 dose, such that APOE4 homozygote women will have the most hippocampal deformation and cognitive loss. We also hypothesize that women who have the APOE4 allele and abnormal CSF A#946, tau or amyloid PET will have the most hippocampal deformation and cognitive decline over time.  The second aim of the GIG Project is to examine the predictive utility of brain morphometry on subsequent cognitive function and clinical progression (CN to MCI or AD, MCI to AD). We hypothesize that hippocampal shape morphometry will predict different rates of cognitive decline and clinical progression between men and women, with accelerated cognitive decline in APOE4 homozygote women. We also hypothesize that women who have the APOE4 allele, brain deformation, and abnormal CSF A#946, tau or amyloid, tau PET will have the most cognitive decline in memory, executive function, and global cognition and the higher rates of       conversion over time.   The last aim of the GIG Project is to conduct exploratory gender x genetic associations with AD risk and analysis of gender x APOE4 associations in ongoing clinical trials paradigms as proof-of-concept. We hypothesize that novel, hypothesis-driven gender-specific associations with other genetic f