AB amyloid_human liver protocols and data.zip

Impaired Hepatic Amyloid-Beta
Degradation in Alzheimer’s Disease.

Chera L. Maarouf1, Jessica E.
Walker1, Lucia I. Sue1, Brittany N. Dugger2, Thomas
G. Beach1 and Geidy E. Serrano1

Banner Sun Health Research Institute, Sun City, AZ,
85351
Department of Pathology and Laboratory Medicine,
University of California Davis School of Medicine Sacramento, CA 95817

Corresponding
author: Geidy E. Serrano, PhD

Banner Sun Health Research Institute

10515
W Santa Fe Drive, Bldg B, 3rd Fl

Sun
City, AZ 85351

Ph:
623-832-5608

Fax: [phone]

email: [e-mail]

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.