Evidence map›Paper›PMID 29158413›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer's disease.

Jay Rasmussen, Jasmin Mahler, Natalie Beschorner, Stephan A Kaeser, Lisa M Häsler, Frank Baumann, Sofie Nyström, Erik Portelius, Kaj Blennow, Tammaryn Lashley and 10 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

144 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  9. The Uppsala APP Mutation Promotes Wild-Type Amyloid-β Aggregation and Deposition In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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84 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

20 authors.

Jay RasmussenDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Jasmin MahlerDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Natalie BeschornerDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Stephan A KaeserDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Lisa M HäslerDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Frank BaumannDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Sofie NyströmDepartment of Physics, Chemistry and Biology, Division of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
Erik PorteliusInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, SE-431 80 Mölndal, Sweden.
Kaj BlennowInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, SE-431 80 Mölndal, Sweden.
Tammaryn LashleyQueen Square Brain Bank for Neurological Diseases, Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 1PJ, United Kingdom.
Nick C FoxDementia Research Centre, University College London, London WC1N 3BG, United Kingdom.
Diego Sepulveda-FallaInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Markus GlatzelInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Adrian L OblakDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202.
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202.
K Peter R NilssonDepartment of Physics, Chemistry and Biology, Division of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
Per HammarströmDepartment of Physics, Chemistry and Biology, Division of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
Matthias StaufenbielDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Lary C WalkerDepartment of Neurology, Emory University, Atlanta, GA 30322.
Mathias JuckerDepartment of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany; mathias.jucker@uni-tuebingen.de.ORCID 0000-0001-9045-1072

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI RENGARAJAN, JYOTHI · 1985 to 2011
$114.0M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
The Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI WALKER, LARY C · 2005 to 2019
$25.7M
ENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8M
NCRR NIH HHS P51 RR000165NIA NIH HHS P30 AG010133NIA NIH HHS P50 AG025688NIH HHS P51 OD011132NINDS NIH HHS P30 NS055077
6 · The paper itself

Abstract

The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-β peptide (Aβ) has been shown to adopt distinct structural conformations with different biological activities, we asked whether Aβ can assume structurally and functionally distinct conformations within the brain. To this end, we analyzed the LCO-stained cores of β-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimer's disease (AD) or sporadic (idiopathic) AD (sAD). The spectral attributes of LCO-bound plaques varied markedly in the brain, but the mean spectral properties of the amyloid cores were generally similar in all three cortical regions of individual patients. Remarkably, the LCO amyloid spectra differed significantly among some of the familial and sAD subtypes, and between typical patients with sAD and those with posterior cortical atrophy AD. Neither the amount of Aβ nor its protease resistance correlated with LCO spectral properties. LCO spectral amyloid phenotypes could be partially conveyed to Aβ plaques induced by experimental transmission in a mouse model. These findings indicate that polymorphic Aβ-amyloid deposits within the brain cluster as clouds of conformational variants in different AD cases. Heterogeneity in the molecular architecture of pathogenic Aβ among individuals and in etiologically distinct subtypes of AD justifies further studies to assess putative links between Aβ conformation and clinical phenotype.

Indexed as

Protein AggregatesAlzheimer DiseaseAmyloidAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsDisease Models, AnimalFemaleFluorescent DyesFrontal LobeGene ExpressionHumansMaleMiceOccipital LobePeptide HydrolasesAmyloidAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAPP protein, humanFluorescent DyesPeptide HydrolasesPresenilin-1Protein AggregatesPSEN1 protein, humanThiophenesAlzheimeramyloidneurodegenerationprionstrains

Identifiers

PMID29158413
PMCPMC5724274

What OpenQuestion holds

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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.