Suppression of Abeta deposition in brain by peripheral administration of Fab fragments of anti-seed antibody.
Assembly and deposition of amyloid beta-protein (Abeta) in the brain is a fundamental process of Alzheimer's disease (AD). We previously hypothesized that GM1 ganglioside-bound Abeta (GAbeta) is an endogenous seed for Abeta assembly in brain. Recently, we have succeeded in generation of a monoclonal antibody specific to GAbeta. Notably, this antibody, 4396C, per se substantially inhibits Abeta assembly in vitro. Here we report that the peripheral administration of Fab fragments of 4396C into transgenic mice expressing a mutant amyloid precursor protein gene, following the conjugation of the protein transduction domain of the Tat protein, markedly suppressed Abeta deposition in the brain. This result further supports our previous hypothesis and also provides a new insight into develop AD therapy through targeting seed Abeta in the brain, which selectively inhibits the initial step of the pathological process of AD.
Yamamoto
Naoki
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu 474-8522, Japan.
Yokoseki
Tatsuki
T
Shibata
Masao
M
Yamaguchi
Haruyasu
H
Yanagisawa
Katsuhiko
K
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D020836:Protein Structure, Quaternary / Q000187:drug effects
D016229:Amyloid beta-Peptides; D015696:Gene Products, tat; D007140:Immunoglobulin Fab Fragments