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dc.contributorSchool of Medicine / Clinical Medicine
dc.contributorSchool of Medicine / Biomedicine
dc.contributor.authorDourlen P
dc.contributor.authorFernandez-Gomez FJ
dc.contributor.authorDupont C
dc.contributor.authorGrenier-Boley B
dc.contributor.authorBellenguez C
dc.contributor.authorObriot H
dc.contributor.authorCaillierez R
dc.contributor.authorSottejeau Y
dc.contributor.authorChapuis J
dc.contributor.authorBretteville A
dc.contributor.authorAbdelfettah F
dc.contributor.authorDelay C
dc.contributor.authorMalmanche N
dc.contributor.authorSoininen H
dc.contributor.authorHiltunen M
dc.contributor.authorGalas MC
dc.contributor.authorAmouyel P
dc.contributor.authorSergeant N
dc.contributor.authorBuée L
dc.contributor.authorLambert JC
dc.contributor.authorDermaut B
dc.date.accessioned2017-04-27T11:17:50Z
dc.date.available2017-04-27T11:17:50Z
dc.date.issued2016
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/2172
dc.description.abstractA recent genome-wide association meta-analysis for Alzheimer’s disease (AD) identified 19 risk loci (in addition to APOE) in which the functional genes are unknown. Using Drosophila, we screened 296 constructs targeting orthologs of 54 candidate risk genes within these loci for their ability to modify Tau neurotoxicity by quantifying the size of >6000 eyes. Besides Drosophila Amph (ortholog of BIN1), which we previously implicated in Tau pathology, we identified p130CAS (CASS4), Eph (EPHA1), Fak (PTK2B) and Rab3-GEF (MADD) as Tau toxicity modulators. Of these, the focal adhesion kinase Fak behaved as a strong Tau toxicity suppressor in both the eye and an independent focal adhesion-related wing blister assay. Accordingly, the human Tau and PTK2B proteins biochemically interacted in vitro and PTK2B co-localized with hyperphosphorylated and oligomeric Tau in progressive pathological stages in the brains of AD patients and transgenic Tau mice. These data indicate that PTK2B acts as an early marker and in vivo modulator of Tau toxicity.
dc.language.isoEN
dc.publisherSpringer Nature
dc.relation.ispartofseriesMOLECULAR PSYCHIATRY
dc.relation.urihttp://dx.doi.org/10.1038/mp.2016.59
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/
dc.titleFunctional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionpublished version
uef.solecris.id41023264
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authors
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/ FP7-ICT/601055/EU/VPH Dementia Research Enabled by IT/ VPH-DARE@IT
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/ FP7-HEALTH/305299/EU/SYSTEMS BIOLOGY OF PATHWAYS INVOLVING BRAIN AGEING/AGEDBRAINSYSBIO
dc.relation.doi10.1038/mp.2016.59
dc.description.reviewstatuspeerReviewed
dc.format.pagerange874–883
dc.relation.issn1359-4184
dc.relation.volume22
dc.rights.accesslevelopenAccess
dc.type.okmA1
dc.type.versioninfo:eu-repo/semantics/publishedVersion


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