ArticleeLife2021
The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer's disease mutations.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- The power of many: when genetics met yeasts and high-throughput.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Discriminating single-amino acid differences and post-translational modifications in negatively charged peptides with α-hemolysin nanopores.Journal of nanobiotechnology · 2026Article
- Nascent protein retention at polysomes reduces kinetic barriers to self-assembly.bioRxiv : the preprint server for biology · 2026Article
- Predicting Peptide Aggregation with Protein Language Model Embeddings.Journal of chemical information and modeling · 2026Article
- Mutational Scanning of α-Synuclein using a Clickable Protein Tag Reveals Determinants of Membrane-Induced Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Massively parallel quantification of mutational impact on IAPP amyloid formation.Nature communications · 2026Article
- Insights into Missense SNPs on Amyloidogenic Proteins.Proteomes · 2025Article
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Employing deep mutational scanning in theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies.bioRxiv : the preprint server for biology · 2025Article
- Massively parallel genetic perturbation suggests the energetic structure of an amyloid-β transition state.Science advances · 2025Article
- Massive mutagenesis reveals an incomplete amyloid motif in Bri2 that turns amyloidogenic upon C-terminal extension.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Massive experimental quantification allows interpretable deep learning of protein aggregation.Science advances · 2025Article
- Massive experimental quantification of amyloid nucleation allows interpretable deep learning of protein aggregation.bioRxiv : the preprint server for biology · 2024Article
- PHACTboost: A Phylogeny-Aware Pathogenicity Predictor for Missense Mutations via Boosting.Molecular biology and evolution · 2024Article
- Fibrinaloid Microclots and Atrial Fibrillation.Biomedicines · 2024Review
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- The Proof-of-Concept of MBA121, a Tacrine-Ferulic Acid Hybrid, for Alzheimer's Disease Therapy.International journal of molecular sciences · 2023Article
- The landscape of tolerated genetic variation in humans and primates.Science (New York, N.Y.) · 2023Article
- mutscan-a flexible R package for efficient end-to-end analysis of multiplexed assays of variant effect data.Genome biology · 2023Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plaques of the amyloid beta (Aß) peptide are a pathological hallmark of Alzheimer's disease (AD), the most common form of dementia. Mutations in Aß also cause familial forms of AD (fAD). Here, we use deep mutational scanning to quantify the effects of >14,000 mutations on the aggregation of Aß. The resulting genetic landscape reveals mechanistic insights into fibril nucleation, including the importance of charge and gatekeeper residues in the disordered region outside of the amyloid core in preventing nucleation. Strikingly, unlike computational predictors and previous measurements, the empirical nucleation scores accurately identify all known dominant fAD mutations in Aß, genetically validating that the mechanism of nucleation in a cell-based assay is likely to be very similar to the mechanism that causes the human disease. These results provide the first comprehensive atlas of how mutations alter the formation of any amyloid fibril and a resource for the interpretation of genetic variation in Aß.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.