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Research Using the NACC Database

Role of cholesterol in amyloid b-induced dysfunction of synaptic transmission
and initiation of neurodegeneration
 
   Lead Investigator:    Qi Zhang
   Institution      :    Vanderbilt University
   E-Mail           :    qi.zhang@vanderbilt.edu
   Proposal ID      :    278



   Proposal Description:
   Synaptic deterioration followed by progressive neurodegeneration occurs at the early stage of Alzheimer???s disease (AD). While Amyloid-beta hypothesis suggests that the aggregation of amyloid-beta initiate the deterioration of synapse, emerging evidence indicates other factors especially cholesterol also contribute to the development of AD. This is further supported by the fact that ApoE, the carrier for cholesterol, is the closest genetic link to AD. Thus, we will test the hypothesis that cholesterol and amyloid-beta have converging impact on synaptic transmission. To do so, we are focusing on three specific aims: (1)Understand the clinic association among ApoE genotype, cholesterol level and dementia in AD patients (2) Understand the impact of abnormal Abeta and cholesterol in synaptic plasticity in animal models of AD (3) Understand the association between Abeta and cholesterol in the degree of synaptic dysfunction and dementia in animal models of AD.