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- Title
Multiple Factors Contribute to the Peripheral Induction of Cerebral ß-Amyloidosis.
- Authors
Eisele, Yvonne S.; Fritschi, Sarah K.; Hamaguchi, Tsuyoshi; Obermüller, Ulrike; Füger, Petra; Skodras, Angelos; Schäfer, Claudia; Odenthal, Jörg; Heikenwalder, Mathias; Staufenbiel, Matthias; Jucker, Mathias
- Abstract
Deposition of aggregated amyloid-ß (Aß) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Aß angiopathy. Experimental evidence supports the concept that Aß multimers can act as seeds and structurally corrupt other Aß peptides by a self-propagating mechanism. Here we compare the induction of cerebral ß-amyloidosis by intraperitoneal applications of Aß-containing brain extracts in three Aß-precursor protein (APP) transgenic mouse lines that differ in levels of transgene expression in brain and periphery (APP23 mice, APP23 mice lacking murine APP, and R1.40 mice). Results revealed that beta-amyloidosis induction, which could be blocked with an anti-Aß antibody, was dependent on the amount of inoculated brain extract and on the level of APP/Aß expression in the brain but not in the periphery. The induced Aß deposits in brain occurred in a characteristic pattern consistent with the entry of Aß seeds at multiple brain locations. Intraperitoneally injected Aß could be detected in blood monocytes and some peripheral tissues (liver, spleen) up to 30 d after the injection but escaped histological and biochemical detection thereafter. These results suggest that intraperitoneally inoculated Aß seeds are transported from the periphery to the brain in which corruptive templating of host Aß occurs at multiple sites, most efficiently in regions with high availability of soluble Aß.
- Subjects
CEREBRAL amyloid angiopathy; PEPTIDES; ALZHEIMER'S disease; AMYLOID beta-protein precursor; TRANSGENIC mice
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 31, p10264
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1608-14.2014