APOE is the strongest genetic risk factor for Alzheimer’s disease, with the APOE4 isoform greatly increasing risk. We still do not completely understand how APOE increases AD risk. We have recently found that APOE4 greatly increases brain degeneration and neuronal loss that is mediated by a key protein in AD, tau, in a mouse model. We will try to better understand how APOE4 is resulting in greater brain damage. In addition, we will determine whether we can decrease APOE levels in the brain and, by doing so, block nerve cell loss and neurodegeneration. If successful, this could lead to new therapeutic approaches to target APOE to prevent the brain damage that leads to dementia in AD.
Understanding the Effect of APOE on Tau-Mediated Neurodegeneration
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