The Role of Kv1.3 Potassium Channel Gene Variants In Alzheimer's Disease 
   Lead Investigator:    Maria Lioudyno
   Institution      :    University of California, Irvine
   E-Mail           :    mlioudyn@uci.edu
   Proposal ID      :    602



   Proposal Description:
   The goal of the proposed study is to analyze the associations between             neuropathologic characteristics (amyloid plaques and neurofibrillary              degeneration scores) and common SNPs at the KCNA3 gene using NACC datasets        linked to NIAGAD???s datasets NG00024 and NG00026. This study is essential to     complete our ongoing analysis of the NG00024 and NG00026 investigating            associations between a common SNP (rs2821557) and dementia parameters in AD and   MCI cohorts.                                                                      Kv1.3 channels, given their pattern of expression in cells and structures         relevant to AD, and their role in the regulation of neuro-immune interaction,     neuronal excitability and neurotrophic mechanisms, are likely to play a major     role in the etiology, onset and specific mechanisms of AD. Revealing the          associations between common KCNA3 SNPs and specific AD neuropathology scores      will provide background for future therapeutic targeting of Kv1.3 for             prevention and/or treatment the AD-associated neurodegeneration.                                                                                                    Specific objectives of the proposed research are:                                 (1) Using the NACC datasets (linked to NIAGADS NG00024 and NG00026), to           summarize the demographic characteristics and available neuropathology data of    the sample by SNP for the following variables: age, sex, clinical dementia, age   of dementia onset, APOE variants, A score (Thal phase for amyloid plaques), B     score (BRAAK stage for neurofibrillary degeneration), and C score (density of     neuritic plaques).                                                                                                                                                  (2) to investigate whether neuropathology scores (A, B , C) are associated with   the rs2821557 and/or other inter