beta-Amyloid peptide vaccination results in marked changes in serum and brain Abeta levels in APPswe/PS1DeltaE9 mice, as detected by SELDI-TOF-based ProteinChip technology.
Although the pathogenesis of Alzheimer's disease (AD) is not fully understood, growing evidence indicates that the deposition of beta-amyloid (Abeta) and the local reactions of various cell types to this protein play major roles in the development of the disease. Immunization with the Abeta 1-42 peptide has been reported to decrease Abeta deposits in the brains of mutant amyloid precursor protein (APP/V717F) transgenic (tg) mice (Schenk et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173-177). We have replicated this finding in APPswe/PS1DeltaE9 tg mice, which also develop Abeta deposits in the brain. The immunized animals developed high titers of antibodies against Abeta 1-42 in serum, and Abeta deposits in the brains were significantly reduced. Using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry and ProteinChip((R)) technology, we detected trends toward increased soluble Abeta peptide in the brain and a decrease in assayable Abeta peptide in the serum of immunized compared with control animals. This last finding raises the possibility that anti-Abeta antibodies in the periphery sequester Abeta peptides or target them for degradation and in this way contribute to the enhanced Abeta clearance from the brain in immunized animals.
Vehmas
A K
AK
Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Borchelt
D R
DR
Price
D L
DL
McCarthy
D
D
Wills-Karp
M
M
Peper
M J
MJ
Rudow
G
G
Luyinbazi
J
J
Siew
L T
LT
Troncoso
J C
JC
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D014612:Vaccines; C075222:amyloid beta-protein (1-42)