The synergic action of amyloid-β peptide and LPS in amyloid plaque formation

Introduction
The current model which assume amyloid-β (Aβ) deposition to be an accidental process resulting from the abnormal behavior of an incidental product of catabolism, is now in contrast with the fact that Aβ, a key player in AD, may have a normal function because belongs to the group of AMPs also called host defense peptide. AMPs such as Aβ, are small molecule peptides which are not only intended to kill pathogens through their antimicrobial activity but they also have a high affinity for bacterial lipopolysaccharide (LPS) or membrane receptors. Once that Aβ is deposited can interact with the LPS which acts as a fibrillogenesis promoter; the positive charge of antibacterial peptides can increase the ability of binding to LPS. The interaction between LPS and Aβ occurs at molecular level, on the basis of their common surfactant properties and considering that detergents and fatty acids are able to form micelles.

Material and methods
SH-SY5Y (neuroblastoma cells) were treated with Aβ_1–42 in the form of monomers at the starting concentration of 10 µg/ml, with LPS dissolved in order to obtain a starting concentration of1 µg/ml and their combination. Each experiment was performed for 24, 48, and 72 h at 37°C. Western blot analysis for Aβ_1-42 monomers, Beclin-1 and Lamp-1; Cytokines (IL-1β) quantification with Elisa; Transmission electron microscopy (TEM) and Statistical analysis were performed.

Results
LPS leads to increased production and impaired degradation of Aβ mediated by upregulation of proinflammatory cytokines and inhibition of Aβ degrading enzyme, respectively intracellular accumulation at the endoplasmic reticulum and in lysosomes; the overexpression of IL-1 occurs at the beginning of the inflammatory process. Over-production of Aβ peptides directed against pathogenic neuroinvasion can cause accumulation of Aβ in plaques; Aβ deposits seem to trigger autophagy.

Conclusions
In this study authors observed the binding of the Aβ spherical oligomers to LPS micellar particles inside neuroblastoma cells, the incorporation of LPS to micellar particles occurs at an early stage of Aβ aggregation acting as a nucleation factor, these results are in agreement with the possibility that microorganisms could play a role in the formation of senile plaques in AD.