In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2021-9-14), p. e3001358-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001358
DOI:
10.1371/journal.pbio.3001358.g001
DOI:
10.1371/journal.pbio.3001358.g002
DOI:
10.1371/journal.pbio.3001358.g003
DOI:
10.1371/journal.pbio.3001358.g004
DOI:
10.1371/journal.pbio.3001358.g005
DOI:
10.1371/journal.pbio.3001358.g006
DOI:
10.1371/journal.pbio.3001358.g007
DOI:
10.1371/journal.pbio.3001358.t001
DOI:
10.1371/journal.pbio.3001358.t002
DOI:
10.1371/journal.pbio.3001358.s001
DOI:
10.1371/journal.pbio.3001358.s002
DOI:
10.1371/journal.pbio.3001358.s003
DOI:
10.1371/journal.pbio.3001358.s004
DOI:
10.1371/journal.pbio.3001358.s005
DOI:
10.1371/journal.pbio.3001358.s006
DOI:
10.1371/journal.pbio.3001358.s007
DOI:
10.1371/journal.pbio.3001358.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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