Significant Upregulation of Alzheimer's β-Amyloid Levels in a Living System Induced by Extracellular Elastin Polypeptides.

Chao Ma,Xintong Yang,Rudolph E Tanzi,Yang Feng,Yao Sun,Juanjuan Su,Hui Wu,Kai Liu,Yingxia Liang,Bo Li,Andreas Herrmann,Nolan Shen,Can Zhang,Hongjie Zhang

doi:10.1002/anie.201912399

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.

Highlights

Alzheimers disease (AD) is a progressive neurodegenerative disorder and the major cause of dementia in the elderly
The elastin-like polypeptides (ELPs) are a family of genetically encoded biopolymers concentration to 200 mg mLÀ1, the transitional point (Tt) shifted to 37 8C and it and contain repeats of canonical sequences derived from further increased to approximate 39 8C when the solution was native elastin
We investigated the interplay of extracellular elastin proteins and Alzheimers amyloid-b peptides (Ab) peptides both in vitro and in vivo

Summary

Introduction

Alzheimers disease (AD) is a progressive neurodegenerative disorder and the major cause of dementia in the elderly. We continued to respectively, were subjected to quantitative WB analysis using investigate the interaction of ELP90 and AD cells at 42 8C the APP8717 antibody and the levels of APPma and APPim and the data indicate a similar trend as the changes observed were the same as controls and no significant difference at 37 8C (Figure 2 D). Our results indicated that there was a significant upregulation in sAPPa levels detected by the 6E10 antibody when comparing ELP-treated groups to the control (p < 0.01, Figure 3 H).

Results

Conclusion