Additional file 6 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 6: Table S4. List of proteins identified in label-free MS analysis of amyloid fibrils isolated from mouse and human cortices following multiprotease digestion. Proteins identified in purified fibrils following their additional multiprotease digestion (N = 8 - 10). Each sheet represents an individual mouse line or human patient data sets, and each row has individual p values using Student’s t test, and adjusted p values with BH correction. Experiment = specific data set, Uniprot accession= Uniprot identifier for each protein, ratio= log2 average NSAF values (purified fibrils/homogenate), t test p value = t test p value, Rank= rank ordered proteins based on p value (if p values are identical, higher ratio was listed first), Adjusted p value is calculated using BH correction, description= protein description

Additional file 2 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 2. Supplementary Materials and Methods

Additional file 8 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 8: Table S6. List of proteins identified in label-free MS analysis of amyloid fibrils isolated from rat hippocampal and cortical neurons incubation recombinant Aβ42 seeds. Proteins identified in fibrils purified from rat cortical and hippocampal neurons (n = four). Proteins identified in least two independent fibril preparations from each culture type (> 4 total, at least 2 cortex + 2 hippocampal) were considered and the table shows only those proteins that were also identified in the TMT analysis of purified amyloid from mouse brains (shown in Table S5). Experiment = specific data set, Uniprot accession = Uniprot identifier for each protein, occurrence score = number of occurrences in independent fibril preparations, description = protein description

Additional file 9 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 9: Table S7. List of proteins identified in label-free MS analysis of amyloid fibrils isolated from Aβ42 fly heads. Proteins identified with significantly higher levels in purified fibrils obtained from Aβ42 flies, compared to control Lac-Z flies (N = four independent biological replicates). In sheet 1, NSAF values for purified fibrils and cortex homogenates for individual proteins were used, each row has individual p values using Student’s t test, followed by adjusted p values with BH correction. Corresponding human and mouse orthologs have been identified for each fly gene (https://www.flyrnai.org/diopt). Sheet 2 shows proteins considered for obtaining RNAi lines following identification of Fly orthologs based on scoring. Sheet 3 and 4 indicates individual severity score and all the analysis performed, Sheet 5 and 6 indicates orthologous human and mouse genes, respectively. Experiment = specific data set, Uniprot accession= Uniprot identifier for each protein, ratio= log2 average NSAF values of purified fibrils (Aβ42 /control flies), protein = protein name, t test p value = t test p value, Rank = rank ordered proteins based on p value (if p values are identical, higher ratio was listed first), Adjusted p value is calculated using BH correction, description= protein description, putative human ortholog = human gene orthologous to the identified fly genes, putative mouse ortholog = mouse gene orthologous to the identified fly genes obtained using Dipot online tool, only high and moderate scoring genes were considered in the analysis). Additional remarks indicate if results (increased abundance in purified fibrils) are statistically significant or not

Additional file 1 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 1: Figure S1. Confirmation of amyloid fibril purification. Figure S2. Aβ38 peptides are present in high abundance in human and mouse fibrils. Figure S3. Effect of Aβ38, Aβ40, and Aβ42 peptides on Aβ38 and Aβ40 amyloid fibril formation in vitro. Figure S4. Comprehensive MS analysis of purified mouse and human fibrils. Figure S5. In vitro and in vivo validation of proteomics data. Figure S6. Metallothionein-3, a metal-binding protein affects amyloid aggregation. Figure S7. Fly orthologues of MS-identified candidate proteins modulate Aβ42-induced neurotoxicity in vivo

Additional file 3 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 3: Table S1. Summary of the human subject brains. Overall, 1 control human brain tissues were used; age, gender, race and other relevant information is provided in sheet 1. For AD human samples, we obtained 13 and 23 human brain tissues with amyloid scores 2 and 3, respectively. All the relevant information are provided for each human sample, including their gender, age, race, postmortem time (PMT), clinical Braak stage, CERAD scores, etc

Additional file 4 of Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity

Additional file 4: Table S2. List of proteins identified in label-free MS analysis of amyloid fibrils isolated from mouse cortices. Proteins identified with a higher abundance in purified fibrils (N = 8) obtained from AppNL-F/NL-F, and AppNL-G-F/NL-G-F, and 5xFAD mouse brains, 6 months age, compared to respective cortex homogenate as input (n = 3 - 4). Average NSAF values for purified fibrils and cortex homogenates for individual proteins were used. Each sheet represents individual mouse genotype, and each row has individual p values using Student’s t test and adjusted p values using Benjamini-Hochberg (BH) correction. Number of proteins with significantly higher levels in AppNL-F/NL-F, and AppNL-G-F/NL-G-F, and 5xFAD brains are 59, 32, and 29, respectively. Experiment = specific data set, Uniprot accession = Uniprot identifier for each protein, ratio = log2 average NSAF values (purified fibrils/homogenate), t test p value = t test p value, Rank = rank ordered proteins based on p value (if p values are identical, higher ratio was listed first). Additional remarks indicate if results (increased abundance in purified fibrils) are statistically significant or not