Abstract
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. This study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in amyloid-β precursor protein (APP)sw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease in Cat D level in APP/PS1/Ctsd+/− compared with APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain. There were also no differences in APP processing, the levels of two other Aβ-degrading proteases, the levels of autophagy related protein, such as LAMP2, P62, LC3-I, LC3-II, and Beclin-1, or the markers of neuroinflammation, observed between the APP/PS1/Ctsd+/+ and APP/PS1/Ctsd+/− mice. Our findings demonstrate that in wild-type mice, Cat D protein levels are either in excess or redundant with other factors in the brain, and at least one allele of Ctsd is dispensable for cerebral β-amyloidosis and autophagy in APP/PS1 transgenic mice. (Figure presented.).
Original language | English (US) |
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Pages (from-to) | 297-304 |
Number of pages | 8 |
Journal | Journal of Neurochemistry |
Volume | 142 |
Issue number | 2 |
DOIs | |
State | Published - Jul 1 2017 |
Bibliographical note
Publisher Copyright:© 2017 International Society for Neurochemistry
Keywords
- Alzheimer's disease
- Amyloid-β
- Cathepsin D
- LAMP2
- LC3
- p62