In the relatively short time allotted, Dale Schenk (519.5) managed to describe most of the data from his group’s recent Nature paper (Nature 1999;400:173-177), and a little more. Schenk demonstrated that Aβ immunization of young (six-week-old) mice, in which treatment had begun before the occurrence of plaque pathology, essentially prevented the development of plaque formation and associated changes. Moreover, immunization of older (11-12 month) mice which already had signs of plaque pathology markedly reduced the extent and halted the progression of the Aβ-mediated pathology typically seen in these mice. As to how immunization produces this effect, Schenk speculated that since these mice have high titer antibodies to Aβ in their serum (and ~0.15% of any given circulating antibody can cross the blood-brain barrier) and immunohistochemistry shows Aβ within microglia in regions where remaining plaques are evident, an Fc-mediated uptake and clearance mechanism is probably responsible both for preventing amyloid plaque formation and for mediating plaque removal.
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- Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999 Jul 8;400(6740):173-7. PubMed.