Affiliations: [a] Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China | [b] Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, China | [c] Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang, China | [d] Reproductive Medicine Department, Liao Ning Regional Hospital of Chinese People's Armed Police Forces, Shenyang, China
Correspondence:
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Correspondence to: Yu-Hua Chen, Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China. Tel.: +86 24 23256666/Ext.5019; Fax: +86 24 23260246; E-mail: [email protected].
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by pathological senile plaques composed of amyloid-β (Aβ) in the cerebral cortex and hippocampus. Bone marrow-derived monocytes of patients with AD migrate across the blood-brain barrier into the brain, but are defective at clearing Aβ in the neuritic plaques. However, the underlying mechanisms remain unclear. Here, in patients with AD, we found that cathepsin D, a major lysosomal aspartic protease, was underexpressed in monocytes, resulting in the defective degradation of Aβ by monocytes/macrophages. Further, downregulation of cathepsin D in THP-1 cells significantly reduced the clearance of amyloid plaques in the brain sections of AβPP/PS1 mice. The clearance ability was recovered by the overexpression of cathepsin D in AD monocytes. These results suggest that decreased expression of cathepsin D in the peripheral monocytes is a potential signature of AD, and that this decreased expression is involved in Aβ degradation and AD pathogenesis.
