Examining phenotypic differences between early- and late-onset Alzheimer?s
disease 
   Lead Investigator:    Thomas Wingo
   Institution      :    Emory University Center for Neurodegenerative Dise
   E-Mail           :    thomas.wingo@emory.edu
   Proposal ID      :    727



   Proposal Description:
   Using data from 32 Alzheimer?s Disease Research Centers maintained by NACC we recently showed that the genetic basis for individuals with Alzheimer?s Disease (AD) with early ages at    onset likely have autosomal recessive causes of their illness, in addition to the known dominant    causes [1]. Further, that data supported the conclusion that the genetic contribution to the    disease declines with increasingly older ages of onset. This proposal aims to determine whether    there are basic phenotypic differences between individuals with younger and older ages of onset    and whether there are phenotypic differences among individuals with early-onset AD.  Specific Aim:    Aim 1: Test the hypothesis that there are phenotypic differences between    individuals with younger and older ages of onset in the NACC dataset.    To do this, we will perform a cox regression models on the outcome variable of age of AD onset    for individuals with either probable or definite AD in the NACC database. Dependent variables    will include those that capture demographic, health history, medication use, physical, and    neurologic symptom the time of disease onset. To decide which variables to include in our    regression analysis, we will first use a simple statistical test of significance (e.g., t-test, ranked    sign test, or Fischer?s exact test depending on the nature of the variable) for a dichotomous    outcome of either early- versus late-onset Alzheimer?s disease.    Aim 2: Test the hypothesis that there are phenotypic differences between    individuals with early-onset AD that likely have autosomal dominant causes of the    illness versus those that likely do not.    Based on our prior work we hypothesize that there are individuals with autosomal recessive    causes of early-onset AD in addition to known dominant causes. One possible way to infer that    there are two groups of early-onset AD sufferers is to determine whether they have distinct    phenotypes. To do this with