Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Synthetic Aβ peptides acquire prion-like properties in the brain

Xiangzhu Xiao, Ignazio Cali, Jue Yuan, Laura Cracco, Paul Curtiss, Liang Zeng, Mai Abouelsaad, Dimitris Gazgalis, Gong-Xian Wang, Qingzhong Kong, Hisashi Fujioka, Gianfranco Puoti and Wen-Quan Zou _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:642-650. https://doi.org/10.18632/oncotarget.2819

Metrics: PDF 1246 views  |   HTML 1389 views  |   ?  


Abstract

Xiangzhu Xiao1,*, Ignazio Cali1,2,7,*, Jue Yuan1, Laura Cracco1,2, Paul Curtiss1, Liang Zeng1,5, Mai Abouelsaad1, Dimitris Gazgalis1, Gong-Xian Wang5, Qingzhong Kong1,3, Hisashi Fujioka6, Gianfranco Puoti1,7 and Wen-Quan Zou1,2,3,4,5

1 Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA

2 National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA

3 Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA

4 National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, Ohio, USA

5 The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, The People’s Republic of China

6 Department of Pharmacology and EM Facility, Case Western Reserve University, Cleveland, Ohio, USA

7 Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy

* These authors contributed equally to this work

Correspondence:

Wen-Quan Zou, email:

Keywords: Alzheimer’s disease, Aβ, prion protein, prion disease, brain, amyloid, electron microscopy

Received: November 11, 2014 Accepted: November 24, 2014 Published: November 25, 2014

Abstract

In transmission studies with Alzheimer’s disease (AD) animal models, the formation of Aβ plaques is proposed to be initiated by seeding the inoculated amyloid β (Aβ) peptides in the brain. Like the misfolded scrapie prion protein (PrPSc) in prion diseases, Aβ in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aβ remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aβ peptides and Aβ isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aβ species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aβ immunoreactivity after digestion with PK. In contrast, synthetic Aβ40 and Aβ42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aβ40 and Aβ42 synthetic peptides shows that both species of Aβ form mature fibrils. Those generated from Aβ40 are longer but less numerous than those made of Aβ42. When spiked into human brain homogenates, both Aβ40 and Aβ42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aβ peptides PrPSc-like physicochemical properties.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 2819