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.
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.
DeMattos
R B
RB
The Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110, USA.
Bales
K R
KR
Cummins
D J
DJ
Dodart
J C
JC
Paul
S M
SM
Holtzman
D M
DM
D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)