Fibril Paint to detect Amyloids and determine Fibril Length

Abstract

AbstractProtein aggregation is related to the development of amyloid diseases, such as Alzheimer’s Disease and Huntington’s Disease. It is of great importance to detect aggregates at the earliest stage possible, which is a prerequisite for early diagnosis. Here, we present a method to monitor protein fibril size from early aggregation steps. We designed a peptide, FibrilPaint1, that specifically recognises and fluorescently labels various fibrils from diseases, but not their monomeric precursors. In combination with Flow Induced Dispersion Analysis, a microfluidics technology, we determined the molecular size of amyloid fibrils with sub-microliter sample volumes. FibrilPaint1 specifically detects structurally unrelated fibrils from Huntingtin and Tau, includingex vivosamples derived from Alzheimer’s Disease, Frontotemporal Dementia and Corticobasal Degeneration patients. The ability to recognise multiple amyloids but not monomeric precursors makes FibrilPaint1 a novel tool for diagnostic applications for amyloid diseases.