ArticleThe Journal of biological chemistry2017
Familial Alzheimer's Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-β Peptide.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 150 citations in OpenAlex.
- Structural Hierarchy and Maturation of Amyloid Fibrils Revealed by Interface Descriptor Analysis.Journal of chemical information and modeling · 2026Article
- Application of artificial intelligence for the prediction of amyloidoses.Neural regeneration research · 2026Article
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Dosa: A method to covalently barcode proteins for high-throughput biochemistry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lysosomal protease-mediated APP degradation is pH-dependent, mutation-sensitive, and facilitates tau proteolysis.Molecular neurodegeneration advances · 2026Article
- Factors Driving Amyloid Beta Fibril Recognition by Cell Surface Receptors: A Computational Study.Molecules (Basel, Switzerland) · 2025Article
- Asparagine Deamidation Attenuates Toxicity, Aggregation, and Microglial Responses of Alzheimer's Amyloid-β.ACS chemical neuroscience · 2025Article
- Decoding adipose-brain crosstalk: Distinct lipid cargo in human adipose-derived extracellular vesicles modulates amyloid aggregation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Dosa: A method to covalently barcode proteins for high throughput biochemistry.bioRxiv : the preprint server for biology · 2025Article
- Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies.bioRxiv : the preprint server for biology · 2025Article
- An approach to predict and inhibit Amyloid Beta dimerization pattern in Alzheimer's disease.Toxicology reports · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Association ofHeliyon · 2024Article
- Review
- MAPT mutations associated with familial tauopathies lead to formation of conformationally distinct oligomers that have cross-seeding ability.Protein science : a publication of the Protein Society · 2024Article
- Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region.Antibodies (Basel, Switzerland) · 2024Article
- Bifurcations in coupled amyloid-β aggregation-inflammation systems.NPJ systems biology and applications · 2024Article
- Computational Study of AmyloidβInorganic chemistry · 2024Article
- Article
- Cryo-EM structures of lipidic fibrils of amyloid-β (1-40).Nature communications · 2024Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Most cases of Alzheimer's disease (AD) are sporadic, but a small percentage of AD cases, called familial AD (FAD), are associated with mutations in presenilin 1, presenilin 2, or the amyloid precursor protein. Amyloid precursor protein mutations falling within the amyloid-β (Aβ) sequence lead to a wide range of disease phenotypes. There is increasing evidence that distinct amyloid structures distinguished by amyloid conformation-dependent monoclonal antibodies have similarly distinct roles in pathology. It is possible that this phenotypic diversity of FAD associated with mutations within the Aβ sequence is due to differences in the conformations adopted by mutant Aβ peptides, but the effects of FAD mutations on aggregation kinetics and conformational and morphological changes of the Aβ peptide are poorly defined. To gain more insight into this possibility, we therefore investigated the effects of 11 FAD mutations on the aggregation kinetics of Aβ, as well as its ability to form distinct conformations recognized by a panel of amyloid conformation-specific monoclonal antibodies. We found that most FAD mutations increased the rate of aggregation of Aβ. The FAD mutations also led to the adoption of alternative amyloid conformations distinguished by monoclonal antibodies and resulted in the formation of distinct aggregate morphologies as determined by transmission electron microscopy. In addition, several of the mutant peptides displayed a large reduction in thioflavin T fluorescence, despite forming abundant fibrils indicating that thioflavin T is a probe of conformational polymorphisms rather than a reliable indicator of fibrillization. Taken together, these results indicate that FAD mutations falling within the Aβ sequence lead to dramatic changes in aggregation kinetics and influence the ability of Aβ to form immunologically and morphologically distinct amyloid structures.
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