An Abeta sequestration approach using non-antibody Abeta binding agents.
Amyloid beta (Abeta) has been considered as a primary cause of Alzheimer's 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.
Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. ym56@georgetown.edu
Yasuji
Y
Matsuoka
Li
L
Shao
Manik
M
Debnath
John
J
Lafrancois
Amanda
A
Becker
Audrey
A
Gray
Paul
P
Aisen
Chester
C
Mathis
William
W
Klunk
Karen
K
Duff
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003224:Congo Red / Q000031:analogs & derivatives* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1; D011485:Protein Binding / Q000502:physiology
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D053764:Presenilin-1; D003224:Congo Red