Elucidating the Molecular Determinants of Aβ Aggregation with Deep Mutational Scanning.

Despite the importance of Aβ aggregation in Alzheimer's disease etiology, our understanding of the sequence determinants of aggregation is sparse and largely derived from studies. For example, proline and alanine scanning mutagenesis of Aβ proposed core regions important for aggregation. However, we lack even this limited mutagenesis data for the more disease-relevant Aβ Thus, to better understand the molecular determinants of Aβ aggregation in a cell-based system, we combined a yeast DHFR aggregation assay with deep mutational scanning.