Induction of cerebral beta-amyloidosis: Intracerebral versus systemic A beta inoculation

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.

Published in:
Proceedings Of The National Academy Of Sciences Of The United States Of America, 106, 12926-12931
National Academy of Sciences

 Record created 2010-03-16, last modified 2018-03-17

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