Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM |
Journal | Proc Natl Acad Sci U S A |
Volume | 98 |
Issue | 15 |
Pagination | 8850-5 |
Date Published | 2001 Jul 17 |
ISSN | 0027-8424 |
Keywords | Alzheimer 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. |
DOI | 10.1073/pnas.151261398 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 11438712 |
PubMed Central ID | PMC37524 |