Plasma amyloid ß levels in Alzheimer's disease and cognitively normal controls in Syrian population.

Background: The pathogenesis of Alzheimer's disease (AD) is believed to be occurred by the production of neurotic plaques of the beta-amyloid peptide (Aß) and deposition of them. Therefore, biomarkers of abnormal Aß processing may represent before the AD clinical biomarkers, which could be benefit for a successful disease management that may prevent the AD development. The aim of this study is to investigate of plasma Aß40,42 levels in Alzheimer's patients in Syria and thus determine whether they may have a potential role as biomarker for identifying and predicting AD. Methods: In this cross-sectional study, the plasma levels of Aß1-40 and Aß1-42 were investigated in two groups represent Syrian population, AD group; clinically diagnosed AD patients (n=50) and CN group; cognitively normal participants (n=33). This study first determined the reference interval of plasma Aß1-40 and Aß1-42 for cognitively normal Syrian. Results were analyzed using SPSS, 24, depending on independent-samples t test, considering that the value of p < 0.05 is statistically significant. Results: The results showed that the plasma levels of Aß1-40 (p<0.001, OR=1.031, 95%CI: 1.012-1.051) and Aß1-42 (p<0.001, OR=1.306, 95%CI: 1.145-1.490) were significantly higher in AD patients than in cognitively normal participants, and no significant association was shown between both of education and sex with plasma Aß levels. Conclusion: The plasma levels of Aß1-40 and Aß1-42 could be potential biomarkers for identifying and predicting AD.

Insertion of the amyloid precursor protein into lipid monolayers: effects of cholesterol and apolipoprotein E.

APP (amyloid precursor protein), together with Chol (cholesterol) and ApoE (apolipoprotein E), has been linked to Alzheimer's disease. We have examined the hypothesis that interaction of APP with the lipid membranes is modulated by Chol and ApoE. Insertion of APP into lipid monolayers was first evidenced as an increase in the surface pressure. APP injected into a subphase induced a substantial increase in the surface pressure of monolayers prepared from PC (L-alpha-phosphatidylcholine), Chol, SPM (sphingomyelin) and PS (L-alpha-phosphatidylserine), the major lipids present in the plasma membranes of brain cells. At a given initial pressure, the insertion of APP into expanded monolayers is higher than that in condensed monolayers, in the order Chol>PC>SPM>PS. The membrane insertion capacity of APP was also measured from surface pressure versus area (pi-A) isotherms of APP-lipid monolayers. The increase in the mean area per molecule in protein-lipid monolayers, in the order PC>Chol>PS>SPM, provides further evidence for protein-lipid interactions. These interactions occurred at optimum salt levels and optimum pH values close to physiological conditions (150 mM NaCl and pH 7.4). In addition, ApoE4 affected the insertion of APP into lipid films. APP-ApoE complexes showed a decreased ability to penetrate lipid monolayers at a constant area. APP-ApoE complexes expanded the pi-A isotherm of a Chol monolayer to a lesser extent than APP alone. These experiments demonstrate the roles of Chol and ApoE in the modulation of membrane insertion of APP.

The amyloid precursor protein interacts with neutral lipids.

The amyloid protein precursor (APP) was incorporated into liposomes or phospholipid monolayers. APP insertion into liposomes required neutral lipids, such as L-alpha-phosphatidylcholine, in the target membrane. It was prevented in vesicles containing L-alpha-phosphatidylserine. The insertion was enhanced in acidic solutions, suggesting that it is modulated by specific charge/charge interactions. Surface-active properties and behaviour of APP were characterized during insertion of the protein in monomolecular films of L-alpha-phosphatidylcholine, L-alpha-phosphatidylethanolamine or L-alpha-phosphatidylserine. The presence of the lipid film enhanced the rate of adsorption of the protein at the interface, and the increase in surface pressure was consistent with APP penetrating the lipid film. The adsorption of APP on the lipid monolayers displayed a significant head group dependency, suggesting that the changes in surface pressure produced by the protein were probably affected by electrostatic interactions with the lipid layers. Our results indicate that the penetration of the protein into the lipid monolayer is also influenced by the hydrophobic interactions between APP and the lipid. CD spectra showed that a large proportion of the alpha-helical secondary structure of APP remained preserved over the pH or ionic strength ranges used. Our findings suggest that APP/membrane interactions are mediated by the lipid composition and depend on both electrostatic and hydrophobic effects, and that the variations observed are not due to major secondary structural changes in APP. These observations may be related to the partitioning of APP into membrane microdomains.