Aβ immunotherapy: Intracerebral sequestration of Aβ by an anti-Aβ monoclonal antibody 266 with high affinity to soluble Aβ

Kaoru Yamada, Chiori Yabuki, Peter Seubert, Dale Schenk, Yukiko Hori, Sumio Ohtsuki, Tetsuya Terasaki, Tadafumi Hashimoto, Takeshi Iwatsubo

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

Amyloid β (Aβ) immunotherapy is emerging as a promising disease-modifying therapy for Alzheimer's disease, although the precise mechanisms whereby anti-Aβ antibodies act against amyloid deposition and cognitive deficits remain elusive. To test the "peripheral sink" theory, which postulates that the effects of anti-Aβ antibodies in the systemic circulation are to promote the Aβ efflux from brain to blood, we studied the clearance of 125I-Aβ1-40 microinjected into mouse brains after intraperitoneal administration of an anti-Aβ monoclonal antibody 266. 125I-Aβ1-40 was rapidly eliminated from brains with a half-life of ∼30 min in control mice, whereas 266 significantly retarded the elimination of Aβ, presumably due to formation of Aβ-antibody complex in brains. Administration of 266 to APP transgenic mice increased the levels of monomer Aβ species in an antibody-bound form, without affecting that of total Aβ. We propose a novel mechanism of Aβ immunotherapy by the class of anti-Aβ antibodies that preferentially bind soluble Aβ, i.e., intracerebral, rather than peripheral, sequestration of soluble, monomer form of Aβ, thereby preventing the accumulation of multimeric toxic Aβ species in brains.

Original languageEnglish
Pages (from-to)11393-11398
Number of pages6
JournalJournal of Neuroscience
Volume29
Issue number36
DOIs
Publication statusPublished - 2009 Sep 9

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Aβ immunotherapy: Intracerebral sequestration of Aβ by an anti-Aβ monoclonal antibody 266 with high affinity to soluble Aβ'. Together they form a unique fingerprint.

Cite this