This document relates to methods and materials for detecting the presence or absence of misfolded polypeptides in a sample. For example, methods and materials for amplifying a sample (e.g., a biological sample or an environmental sample) such that misfolded polypeptides present in the sample can aggregate to form fibrils and/or globular polypeptide aggregates and contacting the amplified sample with a solution containing metal nanoparticles (e.g., gold nanoparticles) or one or more organic dyes (e.g., Congo Red) to detect the presence or absence of fibrils and/or globular polypeptide aggregates are provided. In some cases, methods and materials for determining if a mammal (e.g., a human) has a proteinopathy based, at least in part, in the presence or absence of misfolded polypeptides in a sample obtained from the mammal are provided.