�-Amyloid Peptide Vaccination Results in Marked Changes in Serum and Brain A� Levels in APPswe/PS1?E9 Mice, as Detected by SELDI-TOF-Based ProteinChip[sup �] Technology

Vehmas, Anne K.; Borchelt, David R.; Price, Donald L.; McCarthy, Diane; Wills-Karp, Marsha; Peper, Marilyn J.; Rudow, Gay; Luyinbazi, Jackie; Siew, Lawrence T.; Troncoso, Juan C.
November 2001
DNA & Cell Biology;Nov2001, Vol. 20 Issue 11, p713
Academic Journal
Although the pathogenesis of Alzheimer's disease (AD) is not fully understood, growing evidence indicates that the deposition of �-amyloid (A�) and the local reactions of various cell types to this protein play major roles in the development of the disease. Immunization with the A� 1-42 peptide has been reported to decrease A� deposits in the brains of mutant amyloid precursor protein (APP/V717F) transgenic (tg) mice (Schenk et al. Immunization with amyloid-� attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173�177). We have replicated this finding in APPswe/PS1?E9 tg mice, which also develop A� deposits in the brain. The immunized animals developed high titers of antibodies against A� 1-42 in serum, and A� deposits in the brains were significantly reduced. Using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry and ProteinChip[sup �] technology, we detected trends toward increased soluble A� peptide in the brain and a decrease in assayable A� peptide in the serum of immunized compared with control animals. This last finding raises the possibility that anti-A� antibodies in the periphery sequester A� peptides or target them for degradation and in this way contribute to the enhanced A� clearance from the brain in immunized animals.


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