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)|
|Number of pages||8|
|Journal||Journal of Neurochemistry|
|State||Published - Jul 1 2017|
Bibliographical noteFunding Information:
This work was supported in part by the National Institutes of Health grants NS064090 (JZ), AG031846 (LL), NIH/NIA T32 AG029796 9 (for DAH), the Center on Aging Fesler-Lampert Chair in Aging Studies grant, the College of Pharmacy GAP grant, the Academic Health Center Faculty Research Development Program of the University of Minnesota (LL), U.S. Department of Health and Human Services, and National Institute of Neurological Disorders and Stroke (NS064090). We would like to thank Hailin Lu and Andrea Gram for genotyping and maintaining the mouse colonies. No conflict of interest. All experiments were conducted in compliance with the ARRIVE guidelines.
© 2017 International Society for Neurochemistry
- Alzheimer's disease
- Cathepsin D