Tetrameric N-terminally acetylated α-synuclein is prepared by transforming an expression system with an expression vector encoding α-synuclein, wherein the expression system expresses a native NatB acetylase complex or ortholog thereof and/or wherein an exogenous NatB acetylase complex or ortholog thereof is co-expressed in the expression system, inducing protein expression in the transformed expression system, lysing cells in the transformed expression system to produce a cell lysate, performing salt precipitation of the cell lysate, recovering tetrameric N-terminally acetylated α-synuclein by centrifugation, and purifying the tetrameric N-terminally acetylated α-synuclein. Compositions comprising the same and methods for identifying compounds that stabilize natively folded tetrameric α-synuclein are also provided.