amyloid-beta-peptides and Thrombosis

Amyloid-beta1-40 (Aβ40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein we tested the hypothesis that Aβ40 is deregulated in APS, a systemic autoimmune disease characterized by a thrombo-inflammatory state.. Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 SLE/APS) and 80 age- and sex-matched controls. Plasma Aβ40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aβ40 performance to detect arterial thrombotic APS-related events.. Higher Aβ40 levels were significantly associated with the presence of APS [odds ratio (OR) 1.024 per 1 pg/ml (95% CI 1.007, 1.041)] after adjustment for cardiovascular risk factors (CVRFs), including smoking, arterial hypertension, dyslipidaemia and BMI, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased high-sensitivity CRP (hs-CRP) serum levels was the only independent determinant of Aβ40 levels. Importantly, Aβ40 levels above the optimal receiver operating characteristics (ROC)-derived cut-off value were independently associated with recurrent arterial events [OR 4.93 (95% CI 1.31, 18.51)] after adjustment for age, sex, CVRFs, hs-CRP and high anti-β2 glycoprotein I IgG titres. Finally, by ROC curve analysis, Aβ40 provided incremental additive value over the aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses.. In APS, Aβ40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aβ40 in APS merits further investigation.

Topics: Adult; Amyloid beta-Peptides; Antiphospholipid Syndrome; Biomarkers; C-Reactive Protein; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Peptide Fragments; Thrombosis

The amyloid precursor protein (APP) is found in many cells including neurons, endothelial cells and blood platelets. Beta-amyloid protein (beta AP) is derived from APP and is deposited in brain and in cerebral microvasculature of individuals with Alzheimer's disease. In this study we demonstrate that beta AP interacts with human blood platelets. We found that human beta AP peptide (1-40) fibrils aggregate platelets and support their adhesion, and these interactions are mediated through platelet membrane integrin receptors.

Topics: Alzheimer Disease; Amino Acid Sequence; Amyloid beta-Peptides; Binding Sites; Fibrinogen; Humans; In Vitro Techniques; Macromolecular Substances; Membrane Glycoproteins; Molecular Sequence Data; Oligopeptides; Peptide Fragments; Platelet Adhesiveness; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding; Thrombosis; Thrombospondins