title: Effective screen for amyloid β aggregation inhibitor using amyloid β-conjugated gold nanoparticles.
abstract: The abnormal aggregation of amyloid β (Aβ) and its subsequent intra- and extracellular accumulation constitute the disease-causing cascade of Alzheimer's disease (AD). The detection of Aβ aggregates and senile plaque formation, however, is nearly impossible during early pathogenesis, and the absence of a convenient screen to validate the activity of Aβ aggregation regulators impedes the development of promising drug targets and diagnostic biomarkers for AD. Here, we conjugated amyloid β42 (Aβ42) peptide to gold nanoparticles (AuNPs) to visualize Aβ42 aggregation via Aβ42 aggregation-induced AuNP precipitation. AuNP-Aβ42 precipitate was quantified by optical density measurements of supernatants and thioflavin T binding assay. Transmission electron microscopy (TEM) analysis also showed reduced interparticle distance of AuNPs and confirmed the Aβ42 aggregation-induced AuNP precipitation. Transthyretin, a widely known Aβ aggregation inhibitor, limited AuNP-Aβ42 precipitation by preventing Aβ42 aggregation. Finally, according to TEM analysis, Aβ42-conjugated AuNPs treated with blood-driven serum revealed the differentiated aggregation patterns between normal and AD. These findings may open a scientific breakthrough in finding a possible diagnostic and prognostic tool for neurodegenerative diseases involving abnormal protein aggregation as their key pathogenesis processes.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Jongro-gu, Seoul, Korea.
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Han
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Chang
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jung
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Duk Lyul
authors.initials: DL
authors.lastname: Na
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D000704:Analysis of Variance; D011232:Chemical Precipitation; D055808:Drug Discovery / Q000379:methods*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D013053:Spectrophotometry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011228:Prealbumin; C075222:amyloid beta-protein (1-42); D006046:Gold