Investigation of the Subcellular Neurotoxicity of Amyloid-β Using a Device Integrating Microfluidic Perfusion and Chemotactic Guidance

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

Detail(s)

Original languageEnglish
Article number1600895
Journal / PublicationAdvanced healthcare materials
Volume6
Issue number7
Publication statusPublished - 5 Apr 2017

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder with the histopathological hallmark of extracellular accumulation of amyloid-β (Aβ) peptide in brain senile plaques. Though many studies have shown the neural toxicity from various forms of Aβ peptides, the subcellular mechanisms of Aβ peptide are still not well understood, partially due to the technical challenges of isolating axons or dendrites from the cell body for localized investigation. In this study, the subcellular toxicity and localization of Aβ peptides are investigated by utilizing a microfluidic compartmentalized device, which combines physical restriction and chemotactic guidance to enable the isolation of axons and dendrites for localized pharmacological studies. It is found that Aβ peptides induced neuronal death is mostly resulted from Aβ treatment at cell body or axonal processes, but not at dendritic neurites. Simply applying Aβ to axons alone induces significant hyperactive spiking activity. Dynamic transport of Aβ aggregates is only observed between axon terminal and cell body. In addition to differential cellular uptake, more Aβ-peptide secretion is detected significantly from axons than from dendritic side. These results clearly demonstrate the existence of a localized mechanism in Aβ-induced neurotoxicity, and can potentially benefit the development of new therapeutic strategies for AD.

Research Area(s)

  • Alzheimer's disease, amyloid-beta, microfluidic device, neural guidance, subcellular toxicity

Citation Format(s)

Investigation of the Subcellular Neurotoxicity of Amyloid-β Using a Device Integrating Microfluidic Perfusion and Chemotactic Guidance. / Li, Wei; Xu, Zhen; Xu, Bingzhe; Chan, Chung Yuen; Lin, Xudong; Wang, Ying; Chen, Ganchao; Wang, Zhigang; Yuan, Qiuju; Zhu, Guangyu; Sun, Hongyan; Wu, Wutian; Shi, Peng.

In: Advanced healthcare materials, Vol. 6, No. 7, 1600895, 05.04.2017.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal