Usingmisfolding-prone, cancer-associated variants of human p53 as a modelsystem, we found that strong overexpression conditions, such as highcopy number vectors, strong promoters, high inducer concentrations,and high overexpression temperatures, can yield optimal assay performance.These optimized assay conditions were also validated with additionalMisPs, such as the Alzheimer’s disease-associated amyloid-βpeptide and variants of superoxide dismutase 1 associated with amyotrophiclateral sclerosis. Here, SOD1 is linked to early-onset autosomal dominant Alzheimer disease.