Genetic differences between symptomatic and asymptomatic persons with AD
neuropathologic change
 
   Lead Investigator:    Charlie Mock
   Institution      :    NACC
   E-Mail           :    cmock@uw.edu
   Proposal ID      :    292


   Publications:


1  Monsell SE, Mock C , Fardo DW, Bertelsen S, Cairns NJ, Roe CM, Ellingson S, Morris JC, Goate AM,  Kukull WA
   Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology
   Journal Article  Alzheimer Dis Assoc Disord,31:232-238,2017,PMC5432419

   PUBLISHED



2  Monsell SE, Mock C , Fardo DW, Bertelson S, Cairns NJ, Roe CM, Morris JC, Goate A,  Kukull WA
   Genetic differences between symptomatic and asymptomatic persons with Alzheimer's disease neuropathologic change
   Abstract  Alzheimers Dement,11(7):767,2015,

   PUBLISHED





   Proposal Description:
   In a previous analysis of NACC data we identified demographic and clinical features that were associated with expression of symptoms in the presence of Alzheimer???s disease neuropathologic changes. We defined asymptomatic subjects as having a Clinical Dementia Rating (CDR) global score =0 and symptomatic subjects as having a CDR>0. An interesting finding of this study was that APOE e4 allele status (e4 carrier vs. non-carrier) was associated with the odds of being asymptomatic, even after controlling for the severity of the AD pathology. This finding prompted us to wonder whether other SNPs found to be associated with risk of AD would explain some of the remaining variation in determining whether a subject with AD neuropathology would express clinical symptoms or not. We will be using UDS, NP, and ADGC genotype data to determine if (1) clinically symptomatic and asymptomatic persons with AD neuropathologic change have different allele frequencies for SNPs that have been associated with higher risk of AD and (2) a risk score calculated using the AD risk SNPs and APOE genotype is associated with symptomatic vs. asymptomatic status among those with AD neuropathologic change.