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

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.