Amyloidogenic Nanoplaques in Blood Serum of Patients with Alzheimer's Disease Revealed by Time-Resolved Thioflavin T Fluorescence Intensity Fluctuation Analysis.

摘要: Background Biomarkers are central to current research on molecular mechanisms underlying Alzheimer's disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead onset. also crucial early detection, before clinical manifestation, and new modifying therapies. Objective The overall aim this work develop a minimally invasive method fast, ultra-sensitive cost-effective detection structurally modified peptide/protein self-assemblies in the peripheral blood other biological fluids. Specifically, we focus here using detect structured amyloidogenic oligomeric aggregates serum apparently healthy individuals patients AD stage, measure their concentration size. Methods Time-resolved Thioflavin T (ThT) fluorescence intensity fluctuations sub-femtoliter observation volume element was used identify ThT-active aggregates, hereafter called nanoplaques, with single-particle sensitivity Results size nanoplaques significantly higher diagnosed than control subjects. Conclusion A ultimate, successfully developed. proposed approach neither relies use immune-based probes, nor radiotracers, signal-amplification or protein separation techniques, provides test fast determination peptides/proteins blood, as shown here, but