Significant Upregulation of Alzheimer's β‐Amyloid Levels in a Living System Induced by Extracellular Elastin Polypeptides. Issue 51 (4th November 2019)

• Record Type: Journal Article
• Authors: Ma, Chao; Su, Juanjuan; Sun, Yao; Feng, Yang; Shen, Nolan; Li, Bo; Liang, Yingxia; Yang, Xintong; Wu, Hui; Zhang, Hongjie; Herrmann, Andreas; Tanzi, Rudolph E.; Liu, Kai; Zhang, Can
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 51(2019)
• Page Start: 18703
• Page End: 18709
• Publication Date: 2019-11-04
• Subjects: Alzheimer's disease -- amyloid-β peptides -- extracellular elastin -- upregulation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201912399
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder and the primary cause of age‐related dementia. The etiology of AD is complex and has not been completely elucidated. Herein, we report that treatment with elastin‐like polypeptides (ELPs), a component of the brain extracellular matrix (ECM), significantly increased the levels of AD‐related amyloid‐β peptides (Aβ) both in vitro and in vivo. Regarding the molecular mechanism(s), the upregulation of Aβ levels was related to increased proteolytic processing of the amyloid precursor protein. Furthermore, nesting tests demonstrated that the ELP‐treated animals showed significant neurobehavioral deficits with cognitive impairment. These results suggest that the elastin is associated with AD‐related pathological and behavioral changes. This finding presents a new aspect for Alzheimer's amyloidosis event and provides a great promise in developing ELP‐based model systems to better understand the pathogenesis of AD. Abstract : Treatment with elastin polypeptides, a component of the brain extracellular matrix (ECM), increases levels of β‐amyloid, associated with Alzheimer's disease, both in vitro and in vivo. This is associated with the occurrence of early‐stage cognitive impairment in animals. This provides a new insight into Alzheimer's disease pathogenesis.