| First Author | Eisele YS | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 31 | Pages | 10264-73 |
| PubMed ID | 25080588 | Mgi Jnum | J:223172 |
| Mgi Id | MGI:5648160 | Doi | 10.1523/JNEUROSCI.1608-14.2014 |
| Citation | Eisele YS, et al. (2014) Multiple factors contribute to the peripheral induction of cerebral beta-amyloidosis. J Neurosci 34(31):10264-73 |
| abstractText | Deposition of aggregated amyloid-beta (Abeta) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Abeta angiopathy. Experimental evidence supports the concept that Abeta multimers can act as seeds and structurally corrupt other Abeta peptides by a self-propagating mechanism. Here we compare the induction of cerebral beta-amyloidosis by intraperitoneal applications of Abeta-containing brain extracts in three Abeta-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-Abeta antibody, was dependent on the amount of inoculated brain extract and on the level of APP/Abeta expression in the brain but not in the periphery. The induced Abeta deposits in brain occurred in a characteristic pattern consistent with the entry of Abeta seeds at multiple brain locations. Intraperitoneally injected Abeta 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 Abeta seeds are transported from the periphery to the brain in which corruptive templating of host Abeta occurs at multiple sites, most efficiently in regions with high availability of soluble Abeta. |
