Current safety recommendations for handling mouse and human alpha-synuclein fibrils

α-Synuclein (α-syn) is a 140-amino acid protein that can form amyloid fibrils when misfolded. Aggregated α-syn is the main component of Lewy Bodies and Lewy neurites, pathological markers of synucleinopathies, including Parkinson’s Disease and Dementia with Lewy Bodies. To better understand the role of pathological α-syn in disease, many labs use α-syn preformed fibrils (PFFs) generated from mouse or human recombinant α-syn. The PFFs can be added to neurons in a dish or injected into rodents or primates. Neurons take up the PFFs, which act as seeds to corrupt endogenously expressed α-syn, inducing it to form aggregates very similar to those found in diseased brains. The PFFs are typically generated using recombinant mouse or human α-syn. α-Syn fibrils have also been extracted or amplified from brain tissue extracts, cerebrospinal fluid, or skin biopsies from patients with known synucleinopathy. Pipetting, opening tubes recently removed from the freezer, and sonication of the PFFs to generate fragments could all potentially generate aerosols. Our group consulted with biosafety professionals at the University of Alabama to identify potential risks related to working with α-syn PFFs and offer containment controls to mitigate those risks. The mechanism behind the pathological effect of α-syn remain to be elucidated, but researchers should adhere to strict safety protocols when handling both mouse and human α-syn fibrils to minimize potential exposures. Here, we outline best practices for the safe conduct of research with α-syn fibrils, including personal protective equipment and decontamination procedures. We highlight steps in which extra precautions should be taken, such as during sonication or using sharps, and how to minimize risks.