Impaired hepatic amyloid-beta degradation in Alzheimer’s disease

Extensive research strongly suggests that amyloid beta (Aβ) aggregates in the brain have a central role in Alzheimer's disease (AD) pathogenesis. Pathological Aβ deposition is likely due to an altered balance between overproduction and elimination. Rodent studies have suggested that the liver h...

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Vydáno v:	PloS one Ročník 13; číslo 9; s. e0203659
Hlavní autoři:	Maarouf, Chera L., Walker, Jessica E., Sue, Lucia I., Dugger, Brittany N., Beach, Thomas G., Serrano, Geidy E.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 07.09.2018 Public Library of Science (PLoS)
Témata:	Aged, 80 and over Aging Alzheimer Disease - metabolism Alzheimer's disease Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - metabolism Amyloid beta-protein Apolipoprotein E Biology and Life Sciences Blood & organ donations Blood levels Brain Brain research Cathepsin D Degradation Dementia Development and progression Down syndrome Enzymes Female Fluorescein Gene expression Genetic aspects Genotypes Humans Insulin Insulysin Liver Liver - metabolism Male Medical research Medicine and Health Sciences Neprilysin Neuropathology Pathogenesis Pathology Peptides Physiological aspects Protein Aggregates Proteins Proteolysis Research and Analysis Methods Studies Sucrose Working groups United States United States > US Arizona
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	Extensive research strongly suggests that amyloid beta (Aβ) aggregates in the brain have a central role in Alzheimer's disease (AD) pathogenesis. Pathological Aβ deposition is likely due to an altered balance between overproduction and elimination. Rodent studies have suggested that the liver has a major role in Aβ degradation. It is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. In this study, we hypothesized hepatic Aβ degradation to be impaired in AD subjects. To test our hypothesis, an Aβ degradation assay was developed using synthetic fluorescein-labeled Aβ40 and Aβ42 spiked into human liver homogenates. Aβ degradation rates were lower in AD-derived homogenates as compared with those from non-demented (ND) control subjects, even after accounting for such covariates as age, sex, and APOE genotype. The protein expression of potential Aβ-degrading enzymes were also examined. Neprilysin levels were not different in AD liver samples, while cathepsin D and insulin-degrading enzyme were significantly altered in AD subjects. The results support the possibility that impaired hepatic Aβ degradation could be a factor contributing to increased brain Aβ accumulation and AD.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0203659