Detection of pathological alpha-synuclein aggregates in human iPSC-derived neurons and tissue.

The accumulation of proteins into insoluble aggregates is a common feature of several neurodegenerative diseases. Aggregated α-synuclein is a major component of Lewy bodies that pathologically define Parkinson's disease (PD). Here, we present methods for the detection of pathogenic conformations of α-synuclein in induced pluripotent stem cell (iPSC) patient-derived neuron models and brain tissue. These methods can be applied to studies of PD pathogenesis and the discovery of novel therapeutics that restore physiological α-synuclein. For complete details on the use and execution of this protocol, please refer to Cuddy et al. (2019) and Zunke et al. (2018).