000282580 001__ 282580
000282580 005__ 20251218103443.0
000282580 0247_ $$2doi$$a10.1186/s13024-025-00907-z
000282580 0247_ $$2pmid$$apmid:41327266
000282580 0247_ $$2pmc$$apmc:PMC12667055
000282580 037__ $$aDZNE-2025-01340
000282580 041__ $$aEnglish
000282580 082__ $$a570
000282580 1001_ $$aAndersen, Olav M$$b0
000282580 245__ $$aDomain mapping of disease mutations reveals pathogenic SORL1 variants in Alzheimer's disease.
000282580 260__ $$aLondon$$bBiomed Central$$c2025
000282580 3367_ $$2DRIVER$$aarticle
000282580 3367_ $$2DataCite$$aOutput Types/Journal article
000282580 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1764937864_11988
000282580 3367_ $$2BibTeX$$aARTICLE
000282580 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000282580 3367_ $$00$$2EndNote$$aJournal Article
000282580 520__ $$aProtein truncating variants (PTVs) in SORL1 are observed almost exclusively in Alzheimer’s Disease (AD) cases, but the effect of rare SORL1 missense variants is unclear.To identify high-priority missense variants (HPVs), we applied ‘domain mapping of disease mutations’ for the 637 unique coding SORL1 variants detected in 18,959 AD-cases and 21,893 non-demented controls.In this sample, PTVs and HPVs associated with respectively a 35- and 10-fold increased risk of early onset AD and 17- and 6-fold increased risk of overall AD. The median age at onset (AAO) of PTV- and HPV-carriers was 62 and 64 years, and APOE-genotype contributed to AAO-variability. The median AAO of PTV- and HPV-carriers is ~8–10 years earlier than wild-type SORL1 carriers, matched for APOE-genotype. Specific HPVs are highly penetrant and lead to earlier AAOs than PTVs, suggesting possible dominant negative effects.Our results justify a debate on whether HPV carriers should be considered for clinical counseling.The online version contains supplementary material available at 10.1186/s13024-025-00907-z.
000282580 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000282580 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000282580 650_7 $$2Other$$aAge at onset
000282580 650_7 $$2Other$$aAlzforum mutation database
000282580 650_7 $$2Other$$aAlzheimer’s disease
000282580 650_7 $$2Other$$aDisease risk
000282580 650_7 $$2Other$$aDomain-mapping disease-mutations
000282580 650_7 $$2Other$$aGenetics
000282580 650_7 $$2Other$$aPenetrance
000282580 650_7 $$2Other$$aRare variants
000282580 650_7 $$2Other$$aSORL1
000282580 650_7 $$2Other$$aSORLA
000282580 7001_ $$00000-0001-6746-4326$$ade Waal, Matthijs W J$$b1
000282580 7001_ $$aMonti, Giulia$$b2
000282580 7001_ $$aTesi, Niccolo$$b3
000282580 7001_ $$aJensen, Anne Mette G$$b4
000282580 7001_ $$ade Geus, Christa$$b5
000282580 7001_ $$avan Spaendonk, Rosalina$$b6
000282580 7001_ $$aVogel, Maartje$$b7
000282580 7001_ $$aAhmad, Shahzad$$b8
000282580 7001_ $$aAmin, Najaf$$b9
000282580 7001_ $$aAmouyel, Philippe$$b10
000282580 7001_ $$aBeecham, Gary W$$b11
000282580 7001_ $$aBellenguez, Céline$$b12
000282580 7001_ $$aBerr, Claudine$$b13
000282580 7001_ $$aBis, Joshua C$$b14
000282580 7001_ $$aBoland, Anne$$b15
000282580 7001_ $$aBossù, Paola$$b16
000282580 7001_ $$aBouwman, Femke$$b17
000282580 7001_ $$aBras, Jose$$b18
000282580 7001_ $$aCharbonnier, Camille$$b19
000282580 7001_ $$aClarimon, Jordi$$b20
000282580 7001_ $$aCruchaga, Carlos$$b21
000282580 7001_ $$aDaniele, Antonio$$b22
000282580 7001_ $$aDartigues, Jean-François$$b23
000282580 7001_ $$aDebette, Stéphanie$$b24
000282580 7001_ $$aDeleuze, Jean-François$$b25
000282580 7001_ $$aDenning, Nicola$$b26
000282580 7001_ $$aDeStefano, Anita L$$b27
000282580 7001_ $$aDols-Icardo, Oriol$$b28
000282580 7001_ $$avan Duijn, Cornelia M$$b29
000282580 7001_ $$aFarrer, Lindsay A$$b30
000282580 7001_ $$aFernández, Maria Victoria$$b31
000282580 7001_ $$avan der Flier, Wiesje M$$b32
000282580 7001_ $$aFox, Nick C$$b33
000282580 7001_ $$aGalimberti, Daniela$$b34
000282580 7001_ $$aGenin, Emmanuelle$$b35
000282580 7001_ $$aGille, Johan J P$$b36
000282580 7001_ $$aGrenier-Boley, Benjamin$$b37
000282580 7001_ $$aGrozeva, Detelina$$b38
000282580 7001_ $$aGuen, Yann Le$$b39
000282580 7001_ $$aGuerreiro, Rita$$b40
000282580 7001_ $$aHaines, Jonathan L$$b41
000282580 7001_ $$aHolmes, Clive$$b42
000282580 7001_ $$aHummerich, Holger$$b43
000282580 7001_ $$aArfan Ikram, M.$$b44
000282580 7001_ $$aKamran Ikram, M.$$b45
000282580 7001_ $$aKawalia, Amit$$b46
000282580 7001_ $$aKraaij, Robert$$b47
000282580 7001_ $$aLambert, Jean-Charles$$b48
000282580 7001_ $$aLathrop, Marc$$b49
000282580 7001_ $$aLemstra, Afina W$$b50
000282580 7001_ $$aLleó, Alberto$$b51
000282580 7001_ $$aMyers, Richard M$$b52
000282580 7001_ $$aMannens, Marcel M A M$$b53
000282580 7001_ $$aMarshall, Rachel$$b54
000282580 7001_ $$aMartin, Eden R$$b55
000282580 7001_ $$aMasullo, Carlo$$b56
000282580 7001_ $$aMayeux, Richard$$b57
000282580 7001_ $$aMead, Simon$$b58
000282580 7001_ $$aMecocci, Patrizia$$b59
000282580 7001_ $$aMeggy, Alun$$b60
000282580 7001_ $$aMol, Merel O$$b61
000282580 7001_ $$aNacmias, Benedetta$$b62
000282580 7001_ $$aNaj, Adam C$$b63
000282580 7001_ $$aNapolioni, Valerio$$b64
000282580 7001_ $$aNicholas Cochran, J.$$b65
000282580 7001_ $$aNicolas, Gaël$$b66
000282580 7001_ $$aPasquier, Florence$$b67
000282580 7001_ $$aPastor, Pau$$b68
000282580 7001_ $$aPericak-Vance, Margaret A$$b69
000282580 7001_ $$aPijnenburg, Yolande A L$$b70
000282580 7001_ $$aPiras, Fabrizio$$b71
000282580 7001_ $$aQuenez, Olivier$$b72
000282580 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b73$$udzne
000282580 7001_ $$aRaybould, Rachel$$b74
000282580 7001_ $$aRedon, Richard$$b75
000282580 7001_ $$aReinders, Marcel J T$$b76
000282580 7001_ $$aRichard, Anne-Claire$$b77
000282580 7001_ $$aRiedel-Heller, Steffi G$$b78
000282580 7001_ $$aRivadeneira, Fernando$$b79
000282580 7001_ $$avan Rooij, Jeroen G J$$b80
000282580 7001_ $$aRousseau, Stéphane$$b81
000282580 7001_ $$aRyan, Natalie S$$b82
000282580 7001_ $$aSanchez-Juan, Pascual$$b83
000282580 7001_ $$aSchellenberg, Gerard D$$b84
000282580 7001_ $$aScheltens, Philip$$b85
000282580 7001_ $$aSchott, Jonathan M$$b86
000282580 7001_ $$aSeshadri, Sudha$$b87
000282580 7001_ $$aSie, Daoud$$b88
000282580 7001_ $$aSims, Rebecca$$b89
000282580 7001_ $$aSistermans, Erik A$$b90
000282580 7001_ $$aSorbi, Sandro$$b91
000282580 7001_ $$avan Swieten, John C$$b92
000282580 7001_ $$aTijms, Betty$$b93
000282580 7001_ $$aUitterlinden, André G$$b94
000282580 7001_ $$aVisser, Pieter Jelle$$b95
000282580 7001_ $$0P:(DE-2719)2000057$$aWagner, Michael$$b96$$udzne
000282580 7001_ $$aWallon, David$$b97
000282580 7001_ $$0P:(DE-HGF)0$$aWang, Li-San$$b98
000282580 7001_ $$aWilliams, Julie$$b99
000282580 7001_ $$aYokoyama, Jennifer S$$b100
000282580 7001_ $$aZarea, Aline$$b101
000282580 7001_ $$avan der Lee, Sven J$$b102
000282580 7001_ $$aOlsen, Johan G$$b103
000282580 7001_ $$aHulsman, Marc$$b104
000282580 7001_ $$aHolstege, Henne$$b105
000282580 773__ $$0PERI:(DE-600)2244557-2$$a10.1186/s13024-025-00907-z$$gVol. 20, no. 1, p. 122$$n1$$p122$$tMolecular neurodegeneration$$v20$$x1750-1326$$y2025
000282580 8564_ $$uhttps://pub.dzne.de/record/282580/files/DZNE-2025-01340.pdf$$yOpenAccess
000282580 8564_ $$uhttps://pub.dzne.de/record/282580/files/DZNE-2025-01340.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000282580 909CO $$ooai:pub.dzne.de:282580$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000282580 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812825$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b73$$kDZNE
000282580 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000057$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b96$$kDZNE
000282580 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000282580 9141_ $$y2025
000282580 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bMOL NEURODEGENER : 2022$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bMOL NEURODEGENER : 2022$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-04-10T15:42:51Z
000282580 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-04-10T15:42:51Z
000282580 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000282580 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2025-01-01
000282580 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-01
000282580 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000282580 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-01
000282580 9201_ $$0I:(DE-2719)1011201$$kAG Wagner$$lNeuropsychology$$x0
000282580 9201_ $$0I:(DE-2719)1011101$$kPatient Studies (Bonn)$$lPatient Studies (Bonn)$$x1
000282580 980__ $$ajournal
000282580 980__ $$aVDB
000282580 980__ $$aUNRESTRICTED
000282580 980__ $$aI:(DE-2719)1011201
000282580 980__ $$aI:(DE-2719)1011101
000282580 9801_ $$aFullTexts