Int. J. Mol. Sci. 2013, 14(7), 14908-14922; doi:10.3390/ijms140714908
Review

Proteolytic Cleavage of Apolipoprotein E4 as the Keystone for the Heightened Risk Associated with Alzheimer’s Disease

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Received: 6 June 2013; in revised form: 26 June 2013 / Accepted: 12 July 2013 / Published: 17 July 2013
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by microscopic lesions consisting of beta-amyloid plaques and neurofibrillary tangles (NFTs). The majority of cases are defined as sporadic and are likely caused by a combination of both genetic and environmental factors. Of the genetic risk factors identified, the 34 kDa protein, apolipoprotein (apo) E4, is of significant importance as APOE4 carriers account for 65%–80% of all AD cases. Although apoE4 plays a normal role in lipoprotein transport, how it contributes to AD pathogenesis is currently unknown. One potential mechanism by which apoE4 contributes to disease risk is its propensity to undergo proteolytic cleavage generating N- and C-terminal fragments. The purpose of this review will be to examine the mechanisms by which apoE4 contributes to AD pathogenesis focusing on the potential loss or gain of function that may occur following cleavage of the full-length protein. In this context, a discussion of whether targeting apoE4 therapeutically is a rationale approach to treating this disease will be assessed.
Keywords: apolipoprotein E; apoE4; Alzheimer’s disease; beta amyloid; neurofibrillary tangles; proteolysis; cleavage; neurodegeneration
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MDPI and ACS Style

Rohn, T.T. Proteolytic Cleavage of Apolipoprotein E4 as the Keystone for the Heightened Risk Associated with Alzheimer’s Disease. Int. J. Mol. Sci. 2013, 14, 14908-14922.

AMA Style

Rohn TT. Proteolytic Cleavage of Apolipoprotein E4 as the Keystone for the Heightened Risk Associated with Alzheimer’s Disease. International Journal of Molecular Sciences. 2013; 14(7):14908-14922.

Chicago/Turabian Style

Rohn, Troy T. 2013. "Proteolytic Cleavage of Apolipoprotein E4 as the Keystone for the Heightened Risk Associated with Alzheimer’s Disease." Int. J. Mol. Sci. 14, no. 7: 14908-14922.


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