Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation.

Abstract

Despite the importance of the aberrant polymerization of Abeta in the early pathogenic cascade of Alzheimer's disease, little is known about the induction of Abeta 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 Abeta-containing brain extracts. Once the amyloidogenic process has been exogenously induced, the nature of the induced Abeta-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 Abeta-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 Abeta-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 Abeta-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 Abeta.

• Authors: Yvonne S Eisele, Tristan Bolmont, Mathias Heikenwalder, Franziska Langer, Laura H Jacobson, Zheng-Xin Yan, Klaus Roth, Adriano Aguzzi, Matthias Staufenbiel, Lary C Walker, Mathias Jucker
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 31 Pg. 12926-31 (Aug 04 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19622727 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides

Topics

• Amyloid beta-Peptides (administration & dosage, metabolism)
• Amyloidosis (etiology)
• Animals
• Brain Diseases (etiology)
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Prion Diseases (etiology)