Nature Neuroscience6, 370 - 377 (2003)
Published online: 24 February 2003; | doi:10.1038/nn1022
Extracellular amyloid formation and associated pathology in neural grafts
Melanie Meyer-Luehmann1, 5, Martina Stalder1, 5, Martin C. Herzig1, Stephan A. Kaeser1, Esther Kohler1, Michelle Pfeifer1, Sonia Boncristiano1, Paul M. Mathews2, Marc Mercken3, Dorothee Abramowski4, Matthias Staufenbiel4
& Mathias Jucker1
1
Department of Neuropathology, Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland
2
Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, New York 10962, USA
3
Johnson and Johnson Pharmaceutical Research and Development, B-2340 Beerse, Belgium
4
Novartis Pharma AG, Nervous System Research, CH-4002 Basel, Switzerland
5
The first two authors contributed equally to this work.
Correspondence should be addressed to Mathias Jucker mjucker@uhbs.ch
Amyloid precursor protein (APP) processing and the generation of -amyloid peptide (A) are important in the pathogenesis of Alzheimer's disease. Although this has been studied extensively at the molecular and cellular levels, much less is known about the mechanisms of amyloid accumulation in vivo. We transplanted transgenic APP23 and wild-type B6 embryonic neural cells into the neocortex and hippocampus of both B6 and APP23 mice. APP23 grafts into wild-type hosts did not develop amyloid deposits up to 20 months after grafting. In contrast, both transgenic and wild-type grafts into young transgenic hosts developed amyloid plaques as early as 3 months after grafting. Although largely diffuse in nature, some of the amyloid deposits in wild-type grafts were congophilic and were surrounded by neuritic changes and gliosis, similar to the amyloid-associated pathology previously described in APP23 mice. Our results indicate that diffusion of soluble A in the extracellular space is involved in the spread of A pathology, and that extracellular amyloid formation can lead to neurodegeneration.
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