Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation.
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.
Eisele
Yvonne S
YS
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
Bolmont
Tristan
T
Heikenwalder
Mathias
M
Langer
Franziska
F
Jacobson
Laura H
LH
Yan
Zheng-Xin
ZX
Roth
Klaus
K
Aguzzi
Adriano
A
Staufenbiel
Matthias
M
Walker
Lary C
LC
Jucker
Mathias
M
D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology*; D000818:Animals; D001927:Brain Diseases / Q000209:etiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000209:etiology
D016229:Amyloid beta-Peptides