Journal
JOURNAL OF NEUROCHEMISTRY
Volume 120, Issue 5, Pages 660-666Publisher
WILEY
DOI: 10.1111/j.1471-4159.2011.07551.x
Keywords
Alzheimer; amyloid; prion; proteopathy; senile plaques; transgenic rat
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Funding
- NIH [P51RR-000165, P50AG025688]
- University of Kentucky [1012101660]
- CART Foundation
- Competence Network on Degenerative Dementias [BMBF-01GI0705]
- BMBF in the frame of ERA-Net NEURON (MIPROTRAN)
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Deposition of the amyloid-beta (A beta) peptide in senile plaques and cerebral A beta angiopathy (CAA) can be stimulated in A beta-precursor protein (APP)-transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated A beta seeds. Growing evidence implicates a prion-like mechanism of corruptive protein templating in this phenomenon, in which aggregated A beta itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with A beta seeding have employed animal models that, as they age, eventually will generate A beta lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human APP (APP21 line) does not manifest endogenous deposits of A beta within the course of its median lifespan (30 months). Next, we injected 3-month-old APP21 rats intrahippocampally with dilute Alzheimer brain extracts containing aggregated A beta. After a 9-month incubation period, these rats had developed senile plaques and CAA in the injected hippocampus, whereas control rats remained free of such lesions. These findings underscore the co-dependence of agent and host in governing seeded protein aggregation, and show that cerebral A beta-amyloidosis can be induced even in animals that are relatively refractory to the spontaneous origination of parenchymal and vascular deposits of A beta.
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