期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：31
页码：12926-12931
DOI：10.1073/pnas.0903200106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Despite the importance of the aberrant polymerization of A{beta} in the early pathogenic cascade of Alzheimer's disease, little is known about the induction of A{beta} aggregation in vivo. Here we show that induction of cerebral {beta}-amyloidosis can be achieved in many different brain areas of APP23 transgenic mice through the injection of dilute A{beta}-containing brain extracts. Once the amyloidogenic process has been exogenously induced, the nature of the induced A{beta}-deposition is determined by the brain region of the host. Because these observations are reminiscent of a prion-like mechanism, we then investigated whether cerebral {beta}-amyloidosis also can be induced by peripheral and systemic inoculations or by the intracerebral implantation of stainless steel wires previously coated with minute amounts of A{beta}-containing brain extract. Results reveal that oral, intravenous, intraocular, and intranasal inoculations yielded no detectable induction of cerebral {beta}-amyloidosis in APP23 transgenic mice. In contrast, transmission of cerebral {beta}-amyloidosis through the A{beta}-contaminated steel wires was demonstrated. Notably, plasma sterilization, but not boiling of the wires before implantation, prevented the induction of {beta}-amyloidosis. Our results suggest that minute amounts of A{beta}-containing brain material in direct contact with the CNS can induce cerebral {beta}-amyloidosis, but that systemic cellular mechanisms of prion uptake and transport to the CNS may not apply to A{beta}.
