Background: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering
chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), which in turn could reduce
amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic
environment remains unclear.
Objective: To analyze five chemokines known to be involved in AD in
three different cellular models to better understand the cellular and molecular interactions in the BBB.
Method: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1) were measured in isolated cells, a BBB
model without PBMCs (H4 and hCMEC/D3 cells, a neuroglioma and human endothelial cells, respectively)
and in a complete BBB model with PBMCs from AD patients at a moderate stage. In one set of
experiments, H4 cells were treated with Aβ42.
Results: CCL2 and CCL5 significantly increased in hCMEC/D3 and H4 cells in the complete BBB
model. In turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10 increased
in all cellular actors in the complete BBB model, compared to isolated cells. For CCL4, PBMCs
induced a robust increase in H4 and hCMEC/D3. In turn, the level of CCL4 decreased in PBMCs. Furthermore,
PBMCs triggered a significant increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of
Aβ42 was observed in the complete BBB model.
Conclusion: These findings highlight the interest of a BBB model in order to explore chemokine production.
For the first time, results showed that PBMCs from patients with AD can control the production
of CCL4 and CXCL10 in a human BBB model.