Abstract
Alpha-synuclein (α-Syn) is an important molecule in the pathogenesis of Parkinson's disease and Alzheimer's disease-related dementias such as Lewy body dementia, forming multiple pathological species. In vitro disease models, including human neurons and α-Syn-transfected cells, are instrumental to understand synucleinopathies or test new therapies. Here, we provide a detailed protocol to generate human neurons derived from induced pluripotent stem cells (iPSCs), and HEK cells, with α-Syn mutations. We also describe multiple assays to determine the various α-Syn forms.