Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.
| Autor: | Virginie Lam, Ryusuke Takechi, Mark J Hackett, Roslyn Francis, Michael Bynevelt, Liesl M Celliers, Michael Nesbit, Somayra Mamsa, Frank Arfuso, Sukanya Das, Frank Koentgen, Maree Hagan, Lincoln Codd, Kirsty Richardson, Brenton O'Mara, Rainer K Scharli, Laurence Morandeau, Jonathan Gauntlett, Christopher Leatherday, Jan Boucek, John C L Mamo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | PLoS Biology, Vol 19, Iss 9, p e3001358 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.3001358 |
| Popis: | Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process. |
| Databáze: | Directory of Open Access Journals |
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