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This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

 

 

 

 

 

 

 

Oligomeric Amyloid-β Peptide on 

Sialylic Lewisx–Selectin Bonding 

at Cerebral Endothelial Surface 

 

Sholpan Askarova1, Grace Y. 

Sun2, Gerald A. Meininger3, James 

Lee4 

 
1Center for Life Sciences, Nazarbayev 
University, Astana, Kazakhstan; 
2Department of Biochemistry, University 
of Missouri, USA; 3Dalton Cardiovascular 
Research Center, University of Missouri, 
USA; 4Department of Biological 
Engineeering, University of Missouri, USA 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Vol. 3, Suppl. (2014)   |   ISSN 2166-7403 (online)    

DOI 10.5195/cajgh.2014.150   |   http://cajgh.pitt.edu 

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ASKAROVA 

 

This work is licensed under a Creative Commons Attribution 4.0 United States License. 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 3, Suppl. (2014)  |  ISSN 2166-7403 (online)  |  DOI 10.5195/cajgh.2014.150  |  http://cajgh.pitt.edu 

  

 

Abstract 

Introduction: Alzheimer’s disease (AD) is a chronic neurodegenerative disorder, which affects approximately 10% of the 

population aged 65 and 40% of people over the age 80. Currently, AD is on the list of diseases with no effective treatment. Thus, 

the study of molecular and cellular mechanisms of AD progression is of high scientific and practical importance. In fact, dysfunction 

of the blood-brain barrier (BBB) plays an important role in the onset and progression of the disease. Increased deposition of amyloid 

b peptide (Aβ) in cerebral vasculature and enhanced transmigration of monocytes across the BBB are frequently observed in AD 

brains and are some of the pathological hallmarks of the diseases. Since the transmigration of monocytes across the BBB is both a 

mechanical and a biochemical process, the expression of adhesion molecules and mechanical properties of endothelial cells are the 

critical factors that require investigation. 

Methods: Because of recent advances in the biological applications of atomic force microscopy (AFM), we applied AFM with 

cantilever tips bio-functionalized by sLex in combination with the advanced immunofluorescent microscopy (QIM) to study the 

direct effects of Aβ42 oligomers on the selectins expression, actin polymerization, and cellular mechanical and adhesion properties 

in cerebral endothelial cells (mouse bEnd3 line and primary human CECs) and find a possible way to attenuate these effects.   

Results: QIM results showed that Aβ42 increased the expressions of P-selectin on the cell surface and enhanced actin 

polymerization. Consistent with our QIM results, AFM data showed that Aβ42 increased the probability of cell adhesion with sLex-

coated cantilever and cell stiffness. These effects were counteracted by lovstatin, a cholesterol-lowering drug.  Surprisingly, the 

apparent rupture force of sLex-selectin bonding was significantly lower after treatment with Aβ42, as compared with the control 

(i.e. no treatment). Similar results were also obtained when cells were treated with latruculin A (F-actin-disrupting drug). These 

results suggest that the decrease in the apparent rupture force of sLex-selectin bonding is the consequence of the dissociation of 

adhesion between the cytoskeleton and the bilayer membrane induced by Aβ42. The major causes of excess mortality in the first 

group were neoplams (30.6%), hypertension (23.8%), and myocardial infarction (22.6%). The effects of radiation influenced 

mortality in the second group were 2-2.5 times lower than the first group.   

Conclusion: The studies of the effects of Aβ42 on the adhesion properties of cerebral endothelial cells and how pharmacological 

agents (e.g. statin) counteract these effects should prove to provide insights into the mechanism of inflammation in Alzheimer’s 

brains and the design of therapeutic treatments of the disease.   

Keywords: Alzheimer’s disease, statins, brain inflamation, treatment 

 

 

 

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