(A) In vivo Aß selection assay. Aß fused to the Sup35N domain seeds aggregation of endogenous Sup35p causing a read-through of a premature UGA in the Ade1-14 reporter, allowing the cells to grow in …
(A) Percentage of yeast growth in medium lacking adenine for sup35N, amyloid beta (Aß) and sup35N-Aß constructions. (B) Correlation of nucleation scores for biological replicates 1 and 3 (n = 4,124 …
Raw colony counts from independent testing of the strains expressing the variants reported in Figure 1—figure supplement 1A.
(A and B) Nucleation scores distribution for single (A) and double (B) amino acid (aa) mutants. n = 468 (missense), n = 31 (nonsense), n = 90 (synonymous) for singles, and n = 14,015 (missense) for …
(A) Heatmap of nucleation score categories for single amino acid (aa) variants at different false discovery rates (FDR) (blue: increased nucleation, orange: decreased nucleation, grey: not different …
(A) Effect of single aa mutants on nucleation for each Aß position. The wild-type (WT) aa and position are indicated on the x-axis and coloured on the basis of aa type. The horizontal line indicates …
(A and B) Nucleation scores as a function of aggregation predictors (Tango, Waltz, Zyggregator, and Camsol; Tartaglia and Vendruscolo, 2008; Fernandez-Escamilla et al., 2004; Oliveberg, 2010; Sormann…
Raw colony counts from indepednet testing of the strains expressing the N-terminal truncated varaints reported in Figure 3—figure supplement 1C.
Mutations to other aa are indicated in grey. The wild-type (WT) AA is indicated with ‘*’. The horizontal line indicates WT nucleation score (0). Point size indicates false discovery rate (FDR) (big, …
Receiver operating characteristic (ROC) curves for 12 fAD mutants versus all other single aa mutants in the dataset. Area under the curve (AUC) values are indicated in the legend. Diagonal dashed …
(A and B) Receiver operating characteristic (ROC) curves built using 12 fAD mutants versus all other single amino acid (aa) mutants in the dataset for variant effect predictors (A) and aggregation …
Average effect of mutations visualized on the cross-section of an Aß amyloid fibril (PDB accession 5KK3; Colvin et al., 2016). Nucleation gatekeeper residues and known familial Alzheimer’s disease (f…
Linear organization of the Aß42 and Aß40 fibrils. Disordered/unstructured and structured residues are indicated.
Average effect of mutations visualized on the cross-section of various amyloid beta (Aß) amyloid polymorphs: PDB accession 2BEG (Lührs et al., 2005), 2MXU (Xiao et al., 2015), 5AEF (Schmidt et al., …
Table listing the impact on aggregation rates for 16 Aß42 variants for which these measurements could be retrieved from the literature.
For the same variants, the table also reports nucleation scores, as quantified in this study, and the qualitative agreement or disagreement with the previously published data.
Table listing the mutations in Aß42 that significantly increase nucleation score and that are therefore proposed as novel familial Alzheimer’s disease (fAD) candidates.
For each mutation, the corresponding nucleation score (NS) is reported.
List of oligonucleotides used in this study.
Processed data required to make all analyses and figures in this paper.
Read counts, nucleation scores, and associated error terms are reported for each Aß42 variant in each replicate. See sheet one for a deeper explanation of headers.