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

Journal of Alzheimer's Disease : JAD
Ann TiimanVladana Vukojević

Abstract

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 to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies. The overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size. Time-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size. The concentration and size of structured amyloidogenic nano...Continue Reading

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Citations

Oct 30, 2019·Current Alzheimer Research·Petter JäremoHomira Behbahani
Nov 6, 2020·Quarterly Reviews of Biophysics·Jinming WuJinghui Luo
Jan 26, 2021·Frontiers in Aging Neuroscience·Mari AksnesAnne-Brita Knapskog
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jie YangSi Wu
Jun 9, 2021·Translational Neurodegeneration·Mari AksnesAnne-Brita Knapskog

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Methods Mentioned

BETA
fluorescence spectroscopy
fluorescence
fluorescence correlation spectroscopy
FCS
gastric bypass
enzyme-linked immunosorbent assay
electrophoresis

Software Mentioned

GraphPad

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