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The apoE receptors, ApoER2 and VLDLR, regulate neuronal development and synaptic plasticity in the adult brain through interacting with Reelin. Our lab is currently focused on 1) further characterizing the role of Reelin and lipoprotein receptors in the adult brain and cognitive function, and 2) establishing whether alterations in Reelin signaling are associated with neurodegenerative diseases such as Alzheimer's disease. Specifically, we are using a variety of genetic mouse models and in vivo surgical approaches to explore how changes in Reelin levels affect adult learning and behavior.
Moreover, how the Reelin pathway is affected by carriage of the apoE4 allele, accumulation of neurotoxic abeta, and other neurodegenerative processes has not been previously explored. As a result, we are developing assays to monitor the integrity of the Reelin signaling pathway in vivo, 2) determining how it is affected by critical pathophysiological hallmarks of AD such as Abeta accumulation and tau aggregation, and 3) establishing whether impairments in Reelin signaling are involved in the progression of AD and can be targeted for therapeutic intervention.
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