Novel therapeutic approach for the treatment of Alzheimer's disease by peripheral administration of agents with an affinity to beta-amyloid.
Plaques containing beta-amyloid (Abeta) peptides are one of the pathological features of Alzheimer's disease, and the reduction of Abeta is considered a primary therapeutic target. Amyloid clearance by anti-Abeta antibodies has been reported after immunization, and recent data have shown that the antibodies may act as a peripheral sink for Abeta, thus altering the periphery/brain dynamics. Here we show that peripheral treatment with an agent that has high affinity for Abeta (gelsolin or GM1) but that is unrelated to an antibody or immune modulator reduced the level of Abeta in the brain, most likely because of a peripherally acting effect. We propose that in general, compounds that sequester plasma Abeta 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.
Matsuoka
Yasuji
Y
The Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA. matsuoka@nki.rfmh.org
Saito
Mitsuo
M
LaFrancois
John
J
Saito
Mariko
M
Gaynor
Kate
K
Olm
Vicki
V
Wang
Lili
L
Casey
Evelyn
E
Lu
Yifan
Y
Shiratori
Chiharu
C
Lemere
Cynthia
C
Duff
Karen
K
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D018260:Gelsolin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009154:Mutation; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018260:Gelsolin; D008565:Membrane Proteins; D053764:Presenilin-1; D005677:G(M1) Ganglioside