Research Uncovers Role Of Apolipoprotein E In Alzheimer's Disease

27 October 2004

Inhibiting Apolipoprotein E Possible Means of Therapeutic Intervention for Alzheimer’s Disease

(Tampa, FL) - Johnnie B. Byrd, Sr. Alzheimer’s Center & Research Institute in Tampa, in cooperation with The University of South Florida, announces significant advancements in the means of therapeutic intervention to treat Alzheimer’s Disease (AD).

Led by Huntington Potter, Ph.D. Professor of Biochemistry and Molecular Biology and Pfeiffer Endowed Chair in Alzheimer's Research at USF, and CEO of the Byrd Institute, the researchers have uncovered where the protein Apolipoprotein E exerts its ill affects on Alzheimer's disease.

Research shows that individuals possessing the E4 variant of the protein, Apolipoprotein E (ApoE), is the greatest risk factor for developing Alzheimer’s Disease (AD), besides age. ApoE comes in three different variations E2, E3, and E4, and the progression of AD can be accelerated by over a decade if one has two copies of ApoE4 (humans have two copies of every gene, and can therefore have any combination of the E2, E3, and E4 ApoE variations).

In the first paper*, research by the Byrd Alzheimer’s Center has shown that ApoE impacts amyloid plaque deposition, the major pathological hallmark of Alzheimer’s disease [amyloid plaques are deposits of protein found in the brain of AD patients, and are made primarily of the Amyloid-beta protein (Aß). Specifically, it was found that apoE is responsible for converting Aß into filamentous amyloid such that there is over 3200 times more amyloid in mice with ApoE than those without the gene. Diffuse brain deposits of Aß can occur in the elderly in the absence of AD, and is thought to be a normal aspect of aging, while filamentous amyloid is a pathogenic product of Alzheimer’s disease.

In the second paper**, further studies by the Institute researchers indicate that the process of turning Aß from the diffuse deposition pathway into filamentous amyloid is necessary for inducing cognitive decline. Through spatial memory testing, mice with AD showed cognitive deficits only when the ApoE gene is present.

The implication of these studies is that the amyloid-promoting activity of apoE is essential for the development of both Alzheimer pathology and cognitive decline. Thus, preventing ApoE from acting upon Aß may prove to be an effective means of therapeutic intervention.

Dr. Huntington Potter’s research findings will be published in the October edition of the Journal of Alzheimer’s Disease, Volume 6, p. 509–514 and the October edition of Neurobiology of Aging, Volume 25, p. 1153-1167.

* First Paper: Costa, David A., Nilsson, Lars N. G., Bales, Kelly R., Paul, Steven M., Potter, Huntington. Apolipoprotein E is required for the formation of filamentous amyloid but not for amorphous Aß deposition, in an Aß PP/PS double transgenic mouse model of Alzheimer’s disease. Journal of Alzheimer’s Disease 6 (2004) 509–514

**Second Paper: Nilsson, Lars N. G., Arendash, Gary W., Leighty, Ralph E., Costa, David A., Garcia, Marcos F., Cracciola, Jennifer R., Rojiani, Amyn, Wu, Xin, Bales, Kelly R., Paul, Steven M., Potter, Huntington. Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation. Neurobiology of Aging 25 (2004) 1153–1167

The co-first authors of the papers are David Costa, Lars Nilsson and Gary Arendash, who contributed equally to the work.

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