An Aβ Sequestration Approach Using Non-Antibody Aβ Binding Agents

Title: An Aβ Sequestration Approach Using Non-Antibody Aβ Binding Agents

Volume: 2 Issue: 2

Author(s): Yasuji Matsuoka, Li Shao, Manik Debnath, John LaFrancois, Amanda Becker, Audrey Gray, Paul Aisen, Chester Mathis, William Klunk and Karen Duff

Affiliation:

Keywords: alzheimers disease (ad), immunization, transgenic mice, enoxaparin, brain, dmso, polyethylene glycol

Abstract: Amyloid beta (Abeta) has been considered as a primary cause of Alzheimers disease (AD), and Abeta lowering approaches have been tested. Active immunization against Abeta is one of several promising Abeta-lowering approaches. Two mechanisms have been proposed: enhancement of microglial phagocytosis and Abeta sequestration (also called “peripheral sink”). We hypothesized that Abeta sequestration without immune modulation is sufficient to reduce the brain Abeta load and have demonstrated effective sequestration with Abeta binding agents that do not stimulate an immune reaction. Recent reports from other groups showed two other non-immune related Abeta binding agents, which have no structural relation to compounds we previously tested, reduced brain Abeta after peripheral administration. Congo red is a chemically synthesized small molecule that has binding affinity to Abeta. In the present study, we tested three Congo red derivatives in Abeta plaque-forming mice at an early pathological stage. Unfortunately, peripheral administration for three weeks did not substantially alter brain Abeta load. Optimized Abeta binding agents with high affinity to soluble Abeta are necessary for the sequestration approach.

Cite this article as:

Matsuoka Yasuji, Shao Li, Debnath Manik, LaFrancois John, Becker Amanda, Gray Audrey, Aisen Paul, Mathis Chester, Klunk William and Duff Karen, An Aβ Sequestration Approach Using Non-Antibody Aβ Binding Agents, Current Alzheimer Research 2005; 2 (2) . https://dx.doi.org/10.2174/1567205053585774