Understanding the Basis for the Association of apoE4 with Alzheimers Disease: Opening the Door for Therapeutic Approaches

Author(s): Ning Zhong, Karl H. Weisgraber.

Journal Name: Current Alzheimer Research

Volume 6 , Issue 5 , 2009

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Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimers disease (AD) by an as yet to be defined mechanism. Since the structure or biophysical properties of a protein directly determines function, our approach to addressing mechanism is structure:function based. Domain interaction a structural property of apoE4 that distinguishes it from apoE3 is predicted to contribute to the association of apoE4 with AD. We developed a mouse model, the Arg-61 apoE model, which is specific for domain interaction. These mice display synaptic, functional, and cognitive deficits, demonstrating domain interaction is the causative factor. We present evidence that domain interaction results in stressed astrocytes that are dysfunctional and propose that dysfunctional astrocytes are an early player in apoE4-associated AD and that domain interaction is a potential therapeutic target.

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Article Details

Year: 2009
Page: [415 - 418]
Pages: 4
DOI: 10.2174/156720509789207921
Price: $58

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