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2016 Grants - Nam
Effect of APOE and Amyloid Beta Oligomers Interaction on Cognition Decline in Mice
Kyong Nyon Nam, Ph.D.
University of Pittsburgh
2016 Alzheimer’s Association Research Fellowship (AARF)
How do different versions of apolipoprotein E affect the build-up of beta-amyloid in the brain?
The apolipoprotein E (APOE) gene codes for the production of ApoE protein, a naturally occurring protein in the brain. There are different versions of the APOE gene, and one of those versions, APOE-e4, is known to be a risk factor for Alzheimer’s disease. The more common version, APOE-e3 is not associated with Alzheimer’s risk. It is not yet understood how different versions of the APOE gene, and the proteins they code for, may promote brain changes associated with Alzheimer’s disease. It has been proposed that ApoE4 protein may increase the ability of the protein fragment beta-amyloid to form amyloid plaques, one of the characteristic features of the disease. More research is needed to better understand the molecular mechanisms that may link ApoE and beta-amyloid accumulation in the brain.
In initial studies using nerve cells growing in laboratory dishes, Kyong Nyon Nam, Ph.D., and colleagues found that ApoE4 and ApoE3 differentially impact the formation of beta-amyloid oligomers. Oligomers are small clumps of beta-amyloid that are particularly toxic to nerve cells and are thought to trigger plaque formation. For their current studies, Dr. Nam and team will create “complexes” of beta-amyloid oligomers bound to either ApoE4 or ApoE3 and administer them to mice. They will measure how these different complexes affect plaque formation and memory function. The researchers will also study how different ApoE versions impact the activity of several genes in the brain known to be associated with Alzheimer’s disease.
The results of this work could reveal novel mechanisms that underlie increased Alzheimer’s risk associated with the APOE-e4 genetic variation. These studies could also inform the development of new treatments that target these mechanisms to slow or prevent Alzheimer’s disease in high-risk individuals.