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The Journal of Neuroscience, January 1, 2003, 23(1):29-33

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

Yasuji Matsuoka^{1, 2}, Mitsuo Saito^{1, 2}, John LaFrancois¹, Mariko Saito^{1, 2}, Kate Gaynor¹, Vicki Olm¹, Lili Wang¹, Evelyn Casey¹, Yifan Lu¹, Chiharu Shiratori¹, Cynthia Lemere³, and Karen Duff^{1, 2}

¹ The Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, ² New York University School of Medicine, New York, New York 10016, and ³ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Plaques containing -amyloid (A) peptides are one of the pathological features of Alzheimer's disease, and the reduction of A is considered a primary therapeutic target. Amyloid clearance by anti-A antibodies has been reported after immunization, and recent data have shown that the antibodies may act as a peripheral sink for A, thus altering the periphery/brain dynamics. Here we show that peripheral treatment with an agent that has high affinity for A (gelsolin or GM1) but that is unrelated to an antibody or immune modulator reduced the level of A in the brain, most likely because of a peripherally acting effect. We propose that in general, compounds that sequester plasma A 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.

Key words: Alzheimer's disease; amyloid; A; peripheral sink; sequestration; binding agent

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Copyright © 2003 Society for Neuroscience  0270-6474/03/23129-05$05.00/0

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