Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients

György Várady,Edit Szabó,Ágnes Fehér,Adrienn Németh,Boglárka Zámbó,Magdolna Pákáski,Zoltán Janka,Balázs Sarkadi

doi:10.1016/j.dadm.2015.06.007

Abstract

Preventive measures, prognosis, or selected therapy in multifactorial maladies, including Alzheimer's disease (AD), require the application of a wide range of diagnostic assays. There is a large unmet need for relatively simple, blood-based biomarkers in this regard. We have recently developed a rapid and reliable flow cytometry and antibody-based method for the quantitative measurement of various red blood cell (RBC) membrane proteins from a drop of blood. Here, we document that the RBC expression of certain membrane proteins, especially that of the GLUT1 transporter and the insulin receptor (INSR), is significantly higher in AD patients than in age-matched healthy subjects. The observed differences may reflect long-term metabolic alterations relevant in the development of AD. These findings may pave the way for a diagnostic application of RBC membrane proteins as relatively stable and easily accessible personalized biomarkers in AD.

Highlights

Alzheimer’s disease (AD) is manifested in a progressive dementia that currently affects over 40 million people worldwide
In addition to the general clinical and laboratory examinations, we have examined the expression levels of several transporters and the insulin receptor in the red blood cell (RBC) membranes of normal healthy and AD patients
In early onset AD patients (Fig. 1B), the results showed a significant increase for the RBC membrane expression of GLUT1 and insulin receptor (INSR), whereas we did not find significant alterations in the RBC membrane expression levels for ABCA1, ABCG2, PMCA, and ABCB6 between the early onset AD patients and the age-matched controls

Summary

Introduction

Alzheimer’s disease (AD) is manifested in a progressive dementia that currently affects over 40 million people worldwide. There are no reliable cures or diseasemodifying therapies available, and there is no early diagnostic method to indicate AD before it has progressed to major memory loss and functional decline [1,2]. Current biomarkers for this disease, including cerebrospinal fluid tau and amyloid-b determinations, MRI, and other imaging methods, are invasive, time-consuming, or expensive. The expression and function of RBC membrane proteins for long has been suggested to provide information regarding various disease conditions and were considered as potential biomarkers [4]. In complex metabolic conditions, the RBC adrenergic receptor activation and a related adenosine triphosphate release, the Na-Li countertransport, or the alterations of glucose transport and the insulin receptor have been suggested to correlate with disease susceptibility, treatment response, or complications [5,6]

Methods

Results

Conclusion