Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease.

TitlePeripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2001
AuthorsDeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM
JournalProc Natl Acad Sci U S A
Volume98
Issue15
Pagination8850-5
Date Published2001 Jul 17
ISSN0027-8424
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Antibodies, Monoclonal, Brain, Central Nervous System, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Peptide Fragments
Abstract

Active immunization with the amyloid beta (A beta) peptide has been shown to decrease brain A beta deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-A beta antibodies were shown to mimic this effect. In exploring factors that alter A beta metabolism and clearance, we found that a monoclonal antibody (m266) directed against the central domain of A beta was able to bind and completely sequester plasma A beta. Peripheral administration of m266 to PDAPP transgenic mice, in which A beta is generated specifically within the central nervous system (CNS), results in a rapid 1,000-fold increase in plasma A beta, due, in part, to a change in A beta equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduces A beta deposition, m266 did not bind to A beta deposits in the brain. Thus, m266 appears to reduce brain A beta burden by altering CNS and plasma A beta clearance.

DOI10.1073/pnas.151261398
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11438712
PubMed Central IDPMC37524