Evidence map›Paper›PMID 23175838›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012

The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer's disease.

Megan Larson, Mathew A Sherman, Fatou Amar, Mario Nuvolone, Julie A Schneider, David A Bennett, Adriano Aguzzi, Sylvain E Lesné

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
11.4field-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

172 citing papers in PubMed, 275 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Megan LarsonDepartment of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55414, USA.
Mathew A Sherman
Fatou Amar
Mario Nuvolone
Julie A Schneider
David A Bennett
Adriano Aguzzi
Sylvain E Lesné
University of Minnesota · USRush University Medical Center · USUniversity Hospital of Zurich · CHUniversity of Pavia · IT

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
TOWARD A MODEL OF ALZHEIMERS DISEASER01NS033249 · NINDS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ASHE, KAREN H · 1994 to 2013
$6.5M
PREDOCTORAL TRAINING OF NEUROSCIENTISTST32GM008471 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI EBNER, TIMOTHY J · 1993 to 2017
$4.9M
Mechanism of Action of ABeta*56 in Alzheimer's DiseaseR00AG031293 · NIA · UNIVERSITY OF MINNESOTA · PI LESNE, SYLVAIN E. · 2010 to 2012
$693k
NIA NIH HHS P30 AG010161NIA NIH HHS P30AG10161NIA NIH HHS R00 AG031293NIA NIH HHS R01 AG015819NIA NIH HHS R01AG15819NIGMS NIH HHS T32 GM008471NINDS NIH HHS R01 NS033249
6 · The paper itself

Abstract

Amid controversy, the cellular form of the prion protein PrP(c) has been proposed to mediate oligomeric amyloid-β (Aβ)-induced deficits. In contrast, there is consistent evidence that the Src kinase Fyn is activated by Aβ oligomers and leads to synaptic and cognitive impairment in transgenic animals. However, the molecular mechanism by which soluble Aβ activates Fyn remains unknown. Combining the use of human and transgenic mouse brain tissue as well as primary cortical neurons, we demonstrate that soluble Aβ binds to PrP(c) at neuronal dendritic spines in vivo and in vitro where it forms a complex with Fyn, resulting in the activation of the kinase. Using the antibody 6D11 to prevent oligomeric Aβ from binding to PrP(c), we abolished Fyn activation and Fyn-dependent tau hyperphosphorylation induced by endogenous oligomeric Aβ in vitro. Finally, we showed that gene dosage of Prnp regulates Aβ-induced Fyn/tau alterations. Together, our findings identify a complete signaling cascade linking one specific endogenous Aβ oligomer, Fyn alteration, and tau hyperphosphorylation in cellular and animal models modeling aspects of the molecular pathogenesis of Alzheimer's disease.

Indexed as

Aged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBlotting, WesternCells, CulturedChromatography, GelElectrophoresis, Polyacrylamide GelFemaleGene DeletionGene DosageHumansImmunoprecipitationMaleMiceMice, TransgenicAmyloid beta-PeptidesFYN protein, humanProto-Oncogene Proteins c-fynPrPC Proteinstau Proteins

Identifiers

PMID23175838
PMCPMC3568961
OpenAlexW2155049938

What OpenQuestion holds

Textmetadata
LicenceTDM
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.