Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.
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 gen...
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2021
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oai:doaj.org-article:540be8eaf710424384e6a5c34c3f08312021-12-02T19:54:36ZSynthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.1544-91731545-788510.1371/journal.pbio.3001358https://doaj.org/article/540be8eaf710424384e6a5c34c3f08312021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001358https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Several 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.Virginie LamRyusuke TakechiMark J HackettRoslyn FrancisMichael ByneveltLiesl M CelliersMichael NesbitSomayra MamsaFrank ArfusoSukanya DasFrank KoentgenMaree HaganLincoln CoddKirsty RichardsonBrenton O'MaraRainer K ScharliLaurence MorandeauJonathan GauntlettChristopher LeatherdayJan BoucekJohn C L MamoPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 9, p e3001358 (2021) |
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DOAJ |
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DOAJ |
| language |
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| topic |
Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 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 Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Virginie Lam |
| title |
Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| title_short |
Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| title_full |
Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| title_fullStr |
Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| title_full_unstemmed |
Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype. |
| title_sort |
synthesis of human amyloid restricted to liver results in an alzheimer disease-like neurodegenerative phenotype. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/540be8eaf710424384e6a5c34c3f0831 |
| work_keys_str_mv |
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