Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model.

Mária A Deli,Thierry Janet,Julie Vérité,Adrien Julian,Marc Paccalin,Guylène Page

doi:10.1371/journal.pone.0201232

Abstract

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer’s disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.

Highlights

In the past, the diagnosis of Alzheimer’s disease (AD) could only be suggested according to clinical symptoms, and a definite diagnosis required autopsy confirmation
No differences have been found in the expression of CC chemokine ligand 2 (CCL2) in peripheral blood mononuclear cells (PBMCs) from other groups of patients in the blood brain barrier (BBB) models compared to respective isolated PBMCs cells (Table 1)
We observed a decrease in the expression of CCL2 in PBMCs, hCMEC/D3 cells and U87i cells in the BBB model with PBMCs from moderate AD patients compared to mild AD patients, which could be used as a potential biomarker to discriminate later stages of AD

Summary

Introduction

The diagnosis of Alzheimer’s disease (AD) could only be suggested according to clinical symptoms, and a definite diagnosis required autopsy confirmation.

Methods

Results

Discussion

Conclusion