Cited by 1,452Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.

Oligomeric and Fibrillar Species of Amyloid-β Peptides Differentially Affect Neuronal Viability

Open access

Abstract

Genetic evidence predicts a causative role for amyloid-beta (A beta) in Alzheimer's disease. Recent debate has focused on whether fibrils (amyloid) or soluble oligomers of A beta are the active species that contribute to neurodegeneration and dementia. We developed two aggregation protocols for the consistent production of stable oligomeric or fibrillar preparations of A beta-(1-42). Here we report that oligomers inhibit neuronal viability 10-fold more than fibrils and approximately 40-fold more than unaggregated peptide, with oligomeric A beta-(1-42)-induced inhibition significant at 10 nm. Under A beta-(1-42) oligomer- and fibril-forming conditions, A beta-(1-40) remains predominantly as unassembled monomer and had significantly less effect on neuronal viability than preparations of A beta-(1-42). We applied the aggregation protocols developed for wild type A beta-(1-42) to A beta-(1-42) with the Dutch (E22Q) or Arctic (E22G) mutations. Oligomeric preparations of the mutations exhibited extensive protofibril and fibril formation, respectively, but were not consistently different from wild type A beta-(1-42) in terms of inhibition of neuronal viability. However, fibrillar preparations of the mutants appeared larger and induced significantly more inhibition of neuronal viability than wild type A beta-(1-42) fibril preparations. These data demonstrate that protocols developed to produce oligomeric and fibrillar A beta-(1-42) are useful in distinguishing the structural and functional differences between A beta-(1-42) and A beta-(1-40) and genetic mutations of A beta-(1-42).

Overview

Integrity signals

Registry

Crossref · 10.1074/jbc.m201750200

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Flagged first, then by citations

2 of the 71 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Tagliavini, 1999, Alzheimer Rep., 2, 28
  2. Miravalle, 2000, J. Biol. Chem., 275, 27110, 10.1016/S0021-9258(19)61486-9 · DOI
  3. Sian, 2000, Biochem. J., 349, 299, 10.1042/bj3490299 · DOI

Cited by

Sorted by citations

See all 1,452

Metadata

Authors
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J.
Affiliations
Northwestern University (US)
Corresponding author
LaDu, Mary Jo
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-08
Volume
277
Issue
35
Pages
32046-32053
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2168025729
Cited by
1,452
References
71
Citations by year
2026: 25 · 2025: 33 · 2024: 40 · 2023: 46 · 2022: 45 · 2021: 47 · 2020: 49 · 2019: 55 · 2018: 65 · 2017: 58 · 2016: 61 · 2015: 70 · 2014: 78 · 2013: 86 · 2012: 86
FWCI
22.78
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, amyloid-beta oligomers, amyloid fibrils, Alzheimer's disease, neuronal viability, peptide aggregation, protofibrils, neurotoxicity
MeSH terms
Alzheimer Disease, Cell Survival, Humans, Neuroblastoma, Neurons, Peptide Fragments, Tumor Cells, Cultured, Amyloid beta-Peptides, Microscopy, Atomic Force

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review