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<B>Study of the APOE2 mediated protective effect during mild cognitive impairment
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   Lead Investigator:    Zonghua Li
   Institution      :    Mayo Clinic
   E-Mail           :    Li.Zong@mayo.edu
   Proposal ID      :    1122
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   Proposal Description:
   <textarea name="description" rows="12" cols="85" wrap="virtual" readonly>The e4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD (LOAD), whereas the e2 allele confers the protective effect against AD. However, whether APOE genotype also impacts the conversion from the mild cognitive impairment (MCI) stage to AD is less clear.  This study aims to understand how carrying different APOE genotypes in MCI individuals affect their chances of converting to AD. We hypothesize that 1) APOE4 carriers (E4/E4, E4/E3) have higher while APOE2 carriers (E2/E2, E3/E2) have lower risk of MCI to AD conversion compared with APOE3 homozygous  carriers (E3/E3) 2) APOE genotype impacts differential risk for MCI to AD conversion independent of the amyloid-B? (AB?) deposition. Given that MCI represents the early clinical phase of AD where patients still for the most part have intact cognitive functions, our study may provide invaluable insights as to how to uniquely target this dementia population for therapy.  Objective 1: To obtain the basic statistics for MCI ??? AD conversion    Objective 1.1: We intend to construct a model to describe the progression of AD in relation to AB? deposition (with PiB-PET imaging data) and CSF t-Tau/p-Tau. In addition, we aim to understand how enrolled subjects may fall into different demographic characteristics (gender, races), APOE genotype and MCI/AD status(healthy, MCI-AD conversion, MCI-AD non-conversion) with the Alluvial diagram.    Objective 1.2: We will attempt to identify the predictive factors (demographic characteristics, behavioural factors, biomarkers) for MCI ??? AD conversion via comprehensive correlational analysis combined with machine learning (both supervised and unsupervised learning).    Objective 2: To assess the risk of MCI ??? AD conversion in individuals carrying different APOE genotypes    Objective 2.1: With survival analysis (Cox regression), we will estimate the  median years for MCI ??? AD conversion for individuals carrying different APOE genotypes </textarea>