Apolipoprotein is required for the formation of filamentous amyloid, but not for amorphous Aβ deposition, in an AβPP/PS double transgenic mouse model of Alzheimer's disease

Article type: Research Article

Authors: Costa, David A.^{a; b} | Nilsson, Lars N.G.^c | Bales, Kelly R.^d | Paul, Steven M.^d | Potter, Huntington^{a; b; e; *}

Affiliations: [a] Department of Biochemistry and Molecular Biology and Suncoast Gerontology Center, University of South Florida, Tampa, FL 33620, USA | [b] Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute, 15310 Amberly Dr., Tampa FL, 33647, USA | [c] Department of Public Health and Caring Sciences, Uppsala University, Dag Hammarskjölds Väg 20, S-75185 Uppsala, Sweden | [d] Neuroscience Discovery Research, Lilly Research Laboratories, Indianapolis, Indiana, 46285, USA | [e] H. Lee Moffit Cancer Center and Research Institute, Tampa FL, 33612, USA

Correspondence: [*] Corresponding author: Dr. Huntington Potter, Johnnie B. Byrd Sr. Alzheimer’s Center and Research Institute, Tampa FL 33647, USA. Tel.: +813 866 1600; Fax: +813 866 1601; E-mail: [email protected].

Abstract: To determine the role of apolipoprotein E (apoE) in the deposition of different forms of Alzheimer amyloid deposit, we studied mice expressing both mutant human amyloid β-protein precursor (AβPP) and presenilin 1 (PS1) that, in addition, were either normal or knocked-out for apoE. By 7 months of age, extensive deposits of amorphous amyloid β (Aβ) had developed equally in both lines, indicating that, when present in high amounts, Aβ alone is sufficient for such deposition to occur. In contrast, filamentous, thioflavine S-positive amyloid deposition in AβPP/PS mice was catalyzed at least 3000 fold by apoE. Electron micrographs further illustrated the filamentous nature of Aβ deposits in mice expressing apoE. These and other behavior data indicate that the primary function of apoE in Alzheimer's disease is to promote the polymerization of Aβ into mature, beta pleated sheet filaments, a process that is necessary for inducing cognitive decline. Thus, preventing apoE from binding to Aβ may prove to be an effective means of therapeutic intervention.

Keywords: Alzheimer's disease, amyloid β, amyloid β-protein precursor apolipoprotein E, transgenic mouse model

DOI: 10.3233/JAD-2004-6508

Journal: Journal of Alzheimer's Disease, vol. 6, no. 5, pp. 509-514, 2004