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Apolipoprotein E and Mimetics as Targets and Therapeutics for Alzheimer’s Disease

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Book cover Apolipoprotein Mimetics in the Management of Human Disease

Abstract

After age, the APOE4 genotype is the largest risk factor for Alzheimer’s disease (AD). We have developed a series of novel “COG” peptides that mimic the actions of full-length apolipoprotein-E3. Using multiple approaches, we show that COG1410 crosses the blood-brain barrier to provide anti-inflammatory and neuroprotective activities similar to those associated with APOE2- and APOE3-carrying individuals. Like holo-apoE3, COG112 and COG1410 stimulate neurite outgrowth and provide inhibition of inflammatory cytokine release that is independent of APOE-genotype of the treated cells. Using our CVN mouse model of AD that develops behavioral deficits, neuronal loss, amyloid plaques, and neurofibrillary tangle in a time-dependent manner, treatment with COG1410 significantly improves learning and memory behaviors, while decreasing neuronal loss, decreasing amyloid plaques, and decreasing neurofibrillary tangles. This desirable spectrum of disease ameliorating activities after COG treatments suggests a new approach for the treatment of Alzheimer’s and other APOE4-associated diseases.

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Acknowledgments and Disclosures

Michael P. Vitek, Ph.D., is an Associate Professor of Neurology at Duke University Medical Center, Chief Executive Officer and a stockholder of Cognosci, Inc., and Interim Chief Executive Officer and a stockholder of Oncotide Pharmaceuticals, Inc. Matters pertaining to any institutional or individual conflict of interest are managed by the DUMC Conflict of Interest Committee. Dr. Fengqiao Li is Chief Scientific Officer and a stockholder of Cognosci, Inc. Dr. Carol A. Colton is a Professor of Neurology at Duke University Medical Center where matters pertaining to institutional or individual conflict of interest are managed by the DUMC Conflict of Interest Committee. We would like to thank Ms. M. Jansen for her expert assistance with some experiments presented in this chapter.

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Authors and Affiliations

  1. Department of Neurology and Duke University Medical Center, Cognosci, Inc., Durham, NC, USA

    Michael P. Vitek

  2. Cognosci, Inc., Durham, NC, USA

    Fengqiao Li

  3. Department of Neurology, Duke University Medical Center, Durham, NC, USA

    Carol A. Colton

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  1. Michael P. Vitek
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  2. Fengqiao Li
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  3. Carol A. Colton
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Correspondence to Michael P. Vitek .

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  1. Department of Medicine, University of Alabama School of Medicine, Birmingham, Alabama, USA

    G.M. Anantharamaiah

  2. LipimetiX Development, LLC, Natick, Massachusetts, USA

    Dennis Goldberg

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Vitek, M.P., Li, F., Colton, C.A. (2015). Apolipoprotein E and Mimetics as Targets and Therapeutics for Alzheimer’s Disease. In: Anantharamaiah, G., Goldberg, D. (eds) Apolipoprotein Mimetics in the Management of Human Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-17350-4_11

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