Evidence map›Paper›PMID 22403062›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Antiparallel β-sheet architecture in Iowa-mutant β-amyloid fibrils.

Wei Qiang, Wai-Ming Yau, Yongquan Luo, Mark P Mattson, Robert Tycko

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers.

0numbers the graph read from it
0cells of the map it votes in
185citing papers in PubMed
18.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

185 citing papers in PubMed, 355 citations in OpenAlex.

  1. Article
  2. Article
  3. From Disordered to Ordered: Nanoscale Spectroscopy Reveals Structural Evolution of Amyloid Beta 40 Fibrils.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Chameleonic Nature of Aβ: Implications for Alzheimer's and Other Amyloid Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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 · 2025
    Review
  15. Review
  16. Membrane-assisted Aβ40 aggregation pathways.Cell reports. Physical science · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

125 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Wei QiangLaboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Wai-Ming Yau
Yongquan Luo
Mark P Mattson
Robert Tycko
National Institute of Diabetes and Digestive and Kidney Diseases · USNational Institute on Aging · US

Funding

Structural Studies of Alzheimer's beta-Amyloid FibrilsZIADK029061 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI TYCKO, ROBERT · 2009 to 2025
$8.4M
Intramural NIH HHS
6 · The paper itself

Abstract

Wild-type, full-length (40- and 42-residue) amyloid β-peptide (Aβ) fibrils have been shown by a variety of magnetic resonance techniques to contain cross-β structures in which the β-sheets have an in-register parallel supramolecular organization. In contrast, recent studies of fibrils formed in vitro by the Asp23-to-Asn mutant of 40-residue Aβ (D23N-Aβ(1-40)), which is associated with early onset neurodegeneration, indicate that D23N-Aβ(1-40) fibrils can contain either parallel or antiparallel β-sheets. We report a protocol for producing structurally pure antiparallel D23N-Aβ(1-40) fibril samples and a series of solid state nuclear magnetic resonance and electron microscopy measurements that lead to a specific model for the antiparallel D23N-Aβ(1-40) fibril structure. This model reveals how both parallel and antiparallel cross-β structures can be constructed from similar peptide monomer conformations and stabilized by similar sets of interactions, primarily hydrophobic in nature. We find that antiparallel D23N-Aβ(1-40) fibrils are thermodynamically metastable with respect to conversion to parallel structures, propagate less efficiently than parallel fibrils in seeded fibril growth, and therefore must nucleate more efficiently than parallel fibrils in order to be observable. Experiments in neuronal cell cultures indicate that both antiparallel and parallel D23N-Aβ(1-40) fibrils are cytotoxic. Thus, our antiparallel D23N-Aβ(1-40) fibril model represents a specific "toxic intermediate" in the aggregation process of a disease-associated Aβ mutant.

Indexed as

Alzheimer DiseaseAmyloidAmyloid beta-PeptidesBinding, CompetitiveHumansMagnetic Resonance SpectroscopyMicroscopy, ElectronMicroscopy, Electron, TransmissionModels, BiologicalModels, MolecularMolecular ConformationMutationNeurodegenerative DiseasesPeptide FragmentsThermodynamicsAmyloidAmyloid beta-PeptidesPeptide Fragments

Identifiers

PMID22403062
PMCPMC3311365
OpenAlexW2017684135

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.