RH Logo

82

Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype

Paper Title:

Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype

82

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.

Comments1

Top

Table of contents

Paper PDF

Empty State
This academic paper hasn't been uploaded yet
View the paper now by clicking the link below or upload the PDF
or