title: Analyzing Tau Aggregation with Electron Microscopy.
abstract: Conversion of monomeric tau protein into filamentous aggregates is a defining event in the pathogenesis of Alzheimer's disease. To gain insight into disease pathogenesis, the mechanisms that trigger and mediate tau aggregation are under intense investigation. Characterization efforts have relied primarily on recombinant tau protein preparations and high-throughput solution-based detection methods such as thioflavin-dye fluorescence and laser-light-scattering spectroscopies. Transmission electron microscopy (TEM) is a static imaging tool that complements these approaches by detecting individual tau filaments at nanometer resolution. In doing so, it can provide unique insight into the quality, quantity, and composition of synthetic tau filament populations. Here we describe protocols for analysis of tau filament populations by TEM for purposes of dissecting aggregation mechanism.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Interdisciplinary Biophysics Graduate Program, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Huseby
authors.affiliation: Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, 108 Rightmire Hall, 1060 Carmack Road, Columbus, OH, 43210, USA. kuret.3@osu.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Kuret
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D005456:Fluorescent Dyes; D006801:Humans; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D066263:Protein Aggregation, Pathological; D016875:tau Proteins / Q000737:chemistry / Q000648:ultrastructure*
chemical_list: D005456:Fluorescent Dyes; D016875:tau Proteins
keywords: Aggregation; Electron microscopy; Immunogold labeling; Kinetic analysis; Length distribution