Novel Therapeutic Approach for the Treatment of Alzheimer's Disease by Peripheral Administration of Agents with an Affinity to β-Amyloid

Abstract

Plaques containing β-amyloid (Aβ) peptides are one of the pathological features of Alzheimer's disease, and the reduction of Aβ is considered a primary therapeutic target. Amyloid clearance by anti-Aβ antibodies has been reported after immunization, and recent data have shown that the antibodies may act as a peripheral sink for Aβ, thus altering the periphery/brain dynamics. Here we show that peripheral treatment with an agent that has high affinity for Aβ (gelsolin or GM1) but that is unrelated to an antibody or immune modulator reduced the level of Aβ in the brain, most likely because of a peripherally acting effect. We propose that in general, compounds that sequester plasma Aβ could reduce or prevent brain amyloidosis, which would enable the development of new therapeutic agents that are not limited by the need to penetrate the brain or evoke an immune response.