Neurodegenerative disease research can be considerably accelerated by using fibrillar or oligomeric constructs of prion-like proteins in in vitro or in vivo studies. These exist in a variety of forms, and are able to generate different outcomes depending on how they are prepared. The most popular constructs are pre-formed fibrils (PFFs) of certain proteins, including Alpha Synuclein and Tau, relevant in Parkinson’s and Alzheimer’s Diseases. However, despite being popular in this regard, their preparation – requiring sonication – has not been extensively studied from a phase perspective. In this discussion we examine current best practices and provide direction of why sonication is important and how it affect pre-formed fibrils.