Findings reported in tomorrow’s issue of Nature raise the tantalizing possibility of using vaccination to prevent or ameliorate Alzheimer’s disease. In the study, by Dale Schenk and colleagues at Elan Pharmaceuticals, PDAPP transgenic mice were immunized with synthetic Aβ42. These transgenics, which over-express a gene responsible for an inherited form of Alzheimer’s disease in humans, develop amyloid plaques, astrogliosis and dystrophic neurite as they age. But injections of Aβ42 given at a youthful six weeks essentially prevented these changes as the mice aged. What’s more, when given to 11-month-old mice, which already have well-established pathology, Aβ42 injections significantly reduced the extent and progression of the pathology.
These findings, while intriguing, are just a first step. Many questions and problems need to be addressed before an Alzheimer’s vaccine can even be considered. These transgenic mouse models offer only an incomplete model of the human disease. While they accumulate amyloid in their brains, these mice do not display all of the behavioral, histological or physiological defects seen in AD. Moreover, as Peter St George-Hyslop and David Westaway point out in an accompanying News and Views article, it is not yet known whether extracellular Aβ deposits are causing neuronal dysfunction and death, or are merely a consequence of the disease. What the current study offers is another method by which to test this critical question.—Hakon Heimer
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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.
- St George-Hyslop PH, Westaway DA. Alzheimer's disease. Antibody clears senile plaques. Nature. 1999 Jul 8;400(6740):116-7. PubMed.