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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Bibliographic Details
Published in:PloS one Vol. 13; no. 9; p. e0203659
Main Authors: Maarouf, Chera L., Walker, Jessica E., Sue, Lucia I., Dugger, Brittany N., Beach, Thomas G., Serrano, Geidy E.
Format: Journal Article
Language:English
Published: United States Public Library of Science 07.09.2018
Public Library of Science (PLoS)
Subjects:
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
Online Access:Get full text
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Summary: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.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0203659