β -Amyloid Peptide Vaccination Results in Marked Changes in Serum and Brain A β Levels in APPswe/PS1ΔE9 Mice,as Detected by SELDI-TOF-Based ProteinChip ® Technology

Abstract

Although the pathogenesis of Alzheimer's disease (AD) is not fully understood, growing evidence indicates that the deposition of β-amyloid (Aβ) and the local reactions of various cell types to this protein play major roles in the development of the disease. Immunization with the Aβ 1-42 peptide has been reported to decrease Aβ deposits in the brains of mutant amyloid precursor protein (APP/V717F) transgenic (tg) mice (Schenk et al. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173–177). We have replicated this finding in APPswe/PS1ΔE9 tg mice, which also develop Aβ deposits in the brain. The immunized animals developed high titers of antibodies against Aβ 1-42 in serum, and Aβ deposits in the brains were significantly reduced. Using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry and ProteinChip^® technology, we detected trends toward increased soluble Aβ peptide in the brain and a decrease in assayable Aβ peptide in the serum of immunized compared with control animals. This last finding raises the possibility that anti-Aβ antibodies in the periphery sequester Aβ peptides or target them for degradation and in this way contribute to the enhanced Aβ clearance from the brain in immunized animals.