NR AXPK
AU Jucker,M.; Walker,L.
TI Induction of Cerebral ß-Amyloidosis in Transgenic Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Invited Speakers S4.1
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB The misfolding and aggregation of specific proteins is well-established in the pathogenesis of Alzheimer's disease, but little is known about how protein aggregation is initiated in vivo. We show that intracerebral injection of highly dilute, amyloid-ß (Aß)containing human or APP23 transgenic (tg) mouse brain extract can induce cerebral ßamyloidosis and associated pathology in APP23 tg mice in a time- and concentrationdependent manner. By injecting extracts from APPPS1 tg mice into APP23 hosts and vice versa, our results suggest the occurrence of polymorphic Aß species with varying biological activities, reminiscent of prion strains. Formic acid treatment, but not boiling, abolished the Aß-inducing activity of the extract. Moreover, ß-amyloid-induction was effectively blocked when brain extracts were Aß-immunodepleted, or by Aßimmunization of the host. Notably, intracerebral injections of synthetic Aß preparations in concentrations similar to brain extract levels, as well as cell culture-derived Aß, did not yield significant seeding activity, suggesting that ß-amyloid-induction is dependent on a conformation of Aß that is generated in the in vivo environment. Our results demonstrate that cerebral Aß-amyloidosis can be induced by intracerebral Aß-rich brain extract, and that induction is governed by intrinsic properties of both agent and host. The biochemical nature of the seeding agent and whether peripheral administration of the Aß-rich brain extract can induce cerebral ß-amyloidosis is the focus of ongoing experiments.
AD Mathias Jucker, Hertie Institute of Clinical Brain Research, Department of Cellular Neurology, Germany; Lary Walker, Yerkes National Primate Research Center, USA
SP englisch
PO Schottland