Genetic Architecture of Rate of Decline in Alzheimers Disease

 
   Lead Investigator:    Robert Green
   Institution      :    Brigham  Women's Hospital/Harvard Medical School
   E-Mail           :    rcgreen@genetics.med.harvard.edu
   Proposal ID      :    210


   Publications:


1  Gross AL, Sherva R, Mukherjee SR, Newhouse S, Kauwe J, Saykin AJ, Bennett DA, Chibnik LB, Kraft P, Crane PK, Green RC
   Genome-Wide Association Study of Rate of Cognitive Decline in Six Cohorts with Patients with Alzheimer's Disease
   2013   Abstract  66th GSA Annual Scientific Meeting, New Orleans, LA , 

   ACCEPTED



2  Gross AL, Sherva R, Mukherjee SR, Newhouse S, Waterston LB, Mungas DM, Green RC, Jones RN, Crane PK
   Novel Approach for Calibrating Longitudinal Cognitive Performance in Older Adults
   2013   Abstract  66th GSA Annual Scientific Meeting, New Orleans, LA , 

   ACCEPTED



3  Sherva R, Gross AL, Mukherjee SR, Newhouse S, Kauwe J, Munsie L, Saykin AJ, Bennett DA, Chibnik LB, DeJager P, Kraft P, Crane PK, Green RC
   GWAS of Rate of Cognitive Decline in Six AD Cohorts
   2013   Abstract  63rd Annual Meeting of The American Society of Human Genetics, Boston MA , 

   ACCEPTED





   Proposal Description:
   Alzheimers disease (AD) is a progressive neurological disease that, with the projected aging of the US population, will soon reach epidemic proportions. AD is a dementing illness that inevitably progresses over time, but there is tremendous variability in the rate of disease progression. Some patients with AD have an indolent course, progressing slowly over decades. Others have a more aggressive course, progressing from early symptoms to death in a few years. While correlations between patients with slow vs. rapid course have been studied, there is currently no scientific explanation for the difference between those patients who progress more slowly and those who progress more rapidly. Understanding more about the genetic basis of this variability would help illuminate the biological pathways involved in disease progression and inform the development of strategies for interventions to slow the progression of disease. Identifying genetic markers associated with more rapid or less rapid decline might also help the selection of subjects or inform the interpretation of future clinical trials. Few prior studies have examined genetic associations with rate of decline among AD patients. The goal of this data analysis is to gain insight into the genetic determinants of rate of progression in AD. The results of this data analysis could open entirely new areas of research to understand the pathophysiology of AD, new treatments for AD and new methods in the conduct of clinical trials for AD. Specific Aim 1: To determine if there are genetic factors associated with slower or faster rate of cognitive decline. Hypothesis: Genetic heterogeneity underlies the difference between individuals with AD that progresses slowly vs. rapidly.