Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy in APP/PS1 transgenic mice

Shaowu Cheng, Willayat Y. Wani, David A. Hottman, Angela Jeong, Dongfeng Cao, Kyle J. LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li

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11 Scopus citations


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 languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalJournal of Neurochemistry
Issue number2
StatePublished - Jul 1 2017

Bibliographical note

Publisher Copyright:
© 2017 International Society for Neurochemistry


  • Alzheimer's disease
  • Amyloid-β
  • Cathepsin D
  • LAMP2
  • LC3
  • p62


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