Evidence map›Paper›PMID 25281743›Full record

ArticleThe Journal of biological chemistry2014

Monoclonal antibodies against Aβ42 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain.

Asa Hatami, Ricardo Albay, Sanaz Monjazeb, Saskia Milton, Charles Glabe

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

80 citing papers in PubMed, 125 citations in OpenAlex.

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20 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 2 countries.

Asa HatamiDepartment of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697-3900 and.
Ricardo AlbayDepartment of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697-3900 and.
Sanaz MonjazebDepartment of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697-3900 and.
Saskia MiltonDepartment of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697-3900 and.
Charles GlabeDepartment of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California 92697-3900 and; Biochemistry Department, Faculty of Science and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, 21589 Jeddah, Saudi Arabia. Electronic address: cglabe@uci.edu.
University of California, Irvine · USKing Abdulaziz University · SA

Funding

TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Structure and conformational diversity of amyloid oligomersR01AG033069 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI GLABE, CHARLES G. · 2010 to 2014
$1.4M
NIA NIH HHS AG00538NIA NIH HHS AG 033069NIA NIH HHS P01 AG000538NIA NIH HHS R01 AG033069
6 · The paper itself

Abstract

Amyloidogenic proteins generally form intermolecularly hydrogen-bonded β-sheet aggregates, including parallel, in-register β-sheets (recognized by antiserum OC) or antiparallel β-sheets, β-solenoids, β-barrels, and β-cylindrins (recognized by antiserum A11). Although these groups share many common properties, some amyloid sequences have been reported to form polymorphic structural variants or strains. We investigated the humoral immune response to Aβ42 fibrils and produced 23 OC-type monoclonal antibodies recognizing distinct epitopes differentially associated with polymorphic structural variants. These mOC antibodies define at least 18 different immunological profiles represented in aggregates of amyloid-β (Aβ). All of the antibodies strongly prefer amyloid aggregates over monomer, indicating that they recognize conformational epitopes. Most of the antibodies react with N-terminal linear segments of Aβ, although many recognize a discontinuous epitope consisting of an N-terminal domain and a central domain. Several of the antibodies that recognize linear Aβ segments also react with fibrils formed from unrelated amyloid sequences, indicating that reactivity with linear segments of Aβ does not mean the antibody is sequence-specific. The antibodies display strikingly different patterns of immunoreactivity in Alzheimer disease and transgenic mouse brain and identify spatially and temporally unique amyloid deposits. Our results indicate that the immune response to Aβ42 fibrils is diverse and reflects the structural polymorphisms in fibrillar amyloid structures. These polymorphisms may contribute to differences in toxicity and consequent effects on pathological processes. Thus, a single therapeutic monoclonal antibody may not be able to target all of the pathological aggregates necessary to make an impact on the overall disease process.

Indexed as

alpha-SynucleinAlzheimer DiseaseAmino Acid SequenceAmyloidAmyloid beta-PeptidesAnimalsAntibodies, MonoclonalBrainEpitope MappingEpitopesHot TemperatureHumansHydrogen BondingMiceMice, TransgenicMolecular Sequence Dataalpha-SynucleinAmyloidAmyloid beta-Peptidesamyloid beta-protein (1-42)Antibodies, MonoclonalEpitopesPeptide FragmentsAlzheimer DiseaseAmyloidAβMonoclonal AntibodyPeptide ConformationProtein Aggregation

Identifiers

PMID25281743
PMCPMC4231689
OpenAlexW2155882728

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.