Home > Publications Database > Domain mapping of disease mutations reveals pathogenic SORL1 variants in Alzheimer's disease. > print

001     282580
005     20251218103443.0
024 7 _ |a 10.1186/s13024-025-00907-z
|2 doi
024 7 _ |a pmid:41327266
|2 pmid
024 7 _ |a pmc:PMC12667055
|2 pmc
037 _ _ |a DZNE-2025-01340
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Andersen, Olav M
|b 0
245 _ _ |a Domain mapping of disease mutations reveals pathogenic SORL1 variants in Alzheimer's disease.
260 _ _ |a London
|c 2025
|b Biomed Central
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1764937864_11988
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Protein 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.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Age at onset
|2 Other
650 _ 7 |a Alzforum mutation database
|2 Other
650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a Disease risk
|2 Other
650 _ 7 |a Domain-mapping disease-mutations
|2 Other
650 _ 7 |a Genetics
|2 Other
650 _ 7 |a Penetrance
|2 Other
650 _ 7 |a Rare variants
|2 Other
650 _ 7 |a SORL1
|2 Other
650 _ 7 |a SORLA
|2 Other
700 1 _ |a de Waal, Matthijs W J
|0 0000-0001-6746-4326
|b 1
700 1 _ |a Monti, Giulia
|b 2
700 1 _ |a Tesi, Niccolo
|b 3
700 1 _ |a Jensen, Anne Mette G
|b 4
700 1 _ |a de Geus, Christa
|b 5
700 1 _ |a van Spaendonk, Rosalina
|b 6
700 1 _ |a Vogel, Maartje
|b 7
700 1 _ |a Ahmad, Shahzad
|b 8
700 1 _ |a Amin, Najaf
|b 9
700 1 _ |a Amouyel, Philippe
|b 10
700 1 _ |a Beecham, Gary W
|b 11
700 1 _ |a Bellenguez, Céline
|b 12
700 1 _ |a Berr, Claudine
|b 13
700 1 _ |a Bis, Joshua C
|b 14
700 1 _ |a Boland, Anne
|b 15
700 1 _ |a Bossù, Paola
|b 16
700 1 _ |a Bouwman, Femke
|b 17
700 1 _ |a Bras, Jose
|b 18
700 1 _ |a Charbonnier, Camille
|b 19
700 1 _ |a Clarimon, Jordi
|b 20
700 1 _ |a Cruchaga, Carlos
|b 21
700 1 _ |a Daniele, Antonio
|b 22
700 1 _ |a Dartigues, Jean-François
|b 23
700 1 _ |a Debette, Stéphanie
|b 24
700 1 _ |a Deleuze, Jean-François
|b 25
700 1 _ |a Denning, Nicola
|b 26
700 1 _ |a DeStefano, Anita L
|b 27
700 1 _ |a Dols-Icardo, Oriol
|b 28
700 1 _ |a van Duijn, Cornelia M
|b 29
700 1 _ |a Farrer, Lindsay A
|b 30
700 1 _ |a Fernández, Maria Victoria
|b 31
700 1 _ |a van der Flier, Wiesje M
|b 32
700 1 _ |a Fox, Nick C
|b 33
700 1 _ |a Galimberti, Daniela
|b 34
700 1 _ |a Genin, Emmanuelle
|b 35
700 1 _ |a Gille, Johan J P
|b 36
700 1 _ |a Grenier-Boley, Benjamin
|b 37
700 1 _ |a Grozeva, Detelina
|b 38
700 1 _ |a Guen, Yann Le
|b 39
700 1 _ |a Guerreiro, Rita
|b 40
700 1 _ |a Haines, Jonathan L
|b 41
700 1 _ |a Holmes, Clive
|b 42
700 1 _ |a Hummerich, Holger
|b 43
700 1 _ |a Arfan Ikram, M.
|b 44
700 1 _ |a Kamran Ikram, M.
|b 45
700 1 _ |a Kawalia, Amit
|b 46
700 1 _ |a Kraaij, Robert
|b 47
700 1 _ |a Lambert, Jean-Charles
|b 48
700 1 _ |a Lathrop, Marc
|b 49
700 1 _ |a Lemstra, Afina W
|b 50
700 1 _ |a Lleó, Alberto
|b 51
700 1 _ |a Myers, Richard M
|b 52
700 1 _ |a Mannens, Marcel M A M
|b 53
700 1 _ |a Marshall, Rachel
|b 54
700 1 _ |a Martin, Eden R
|b 55
700 1 _ |a Masullo, Carlo
|b 56
700 1 _ |a Mayeux, Richard
|b 57
700 1 _ |a Mead, Simon
|b 58
700 1 _ |a Mecocci, Patrizia
|b 59
700 1 _ |a Meggy, Alun
|b 60
700 1 _ |a Mol, Merel O
|b 61
700 1 _ |a Nacmias, Benedetta
|b 62
700 1 _ |a Naj, Adam C
|b 63
700 1 _ |a Napolioni, Valerio
|b 64
700 1 _ |a Nicholas Cochran, J.
|b 65
700 1 _ |a Nicolas, Gaël
|b 66
700 1 _ |a Pasquier, Florence
|b 67
700 1 _ |a Pastor, Pau
|b 68
700 1 _ |a Pericak-Vance, Margaret A
|b 69
700 1 _ |a Pijnenburg, Yolande A L
|b 70
700 1 _ |a Piras, Fabrizio
|b 71
700 1 _ |a Quenez, Olivier
|b 72
700 1 _ |a Ramirez, Alfredo
|0 P:(DE-2719)2812825
|b 73
|u dzne
700 1 _ |a Raybould, Rachel
|b 74
700 1 _ |a Redon, Richard
|b 75
700 1 _ |a Reinders, Marcel J T
|b 76
700 1 _ |a Richard, Anne-Claire
|b 77
700 1 _ |a Riedel-Heller, Steffi G
|b 78
700 1 _ |a Rivadeneira, Fernando
|b 79
700 1 _ |a van Rooij, Jeroen G J
|b 80
700 1 _ |a Rousseau, Stéphane
|b 81
700 1 _ |a Ryan, Natalie S
|b 82
700 1 _ |a Sanchez-Juan, Pascual
|b 83
700 1 _ |a Schellenberg, Gerard D
|b 84
700 1 _ |a Scheltens, Philip
|b 85
700 1 _ |a Schott, Jonathan M
|b 86
700 1 _ |a Seshadri, Sudha
|b 87
700 1 _ |a Sie, Daoud
|b 88
700 1 _ |a Sims, Rebecca
|b 89
700 1 _ |a Sistermans, Erik A
|b 90
700 1 _ |a Sorbi, Sandro
|b 91
700 1 _ |a van Swieten, John C
|b 92
700 1 _ |a Tijms, Betty
|b 93
700 1 _ |a Uitterlinden, André G
|b 94
700 1 _ |a Visser, Pieter Jelle
|b 95
700 1 _ |a Wagner, Michael
|0 P:(DE-2719)2000057
|b 96
|u dzne
700 1 _ |a Wallon, David
|b 97
700 1 _ |a Wang, Li-San
|0 P:(DE-HGF)0
|b 98
700 1 _ |a Williams, Julie
|b 99
700 1 _ |a Yokoyama, Jennifer S
|b 100
700 1 _ |a Zarea, Aline
|b 101
700 1 _ |a van der Lee, Sven J
|b 102
700 1 _ |a Olsen, Johan G
|b 103
700 1 _ |a Hulsman, Marc
|b 104
700 1 _ |a Holstege, Henne
|b 105
773 _ _ |a 10.1186/s13024-025-00907-z
|g Vol. 20, no. 1, p. 122
|0 PERI:(DE-600)2244557-2
|n 1
|p 122
|t Molecular neurodegeneration
|v 20
|y 2025
|x 1750-1326
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/282580/files/DZNE-2025-01340.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/282580/files/DZNE-2025-01340.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:282580
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 73
|6 P:(DE-2719)2812825
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 96
|6 P:(DE-2719)2000057
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
914 1 _ |y 2025
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2025-01-01
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b MOL NEURODEGENER : 2022
|d 2025-01-01
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b MOL NEURODEGENER : 2022
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2024-04-10T15:42:51Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2024-04-10T15:42:51Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-01-01
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-01-01
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2025-01-01
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2025-01-01
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-01-01
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-01-01
920 1 _ |0 I:(DE-2719)1011201
|k AG Wagner
|l Neuropsychology
|x 0
920 1 _ |0 I:(DE-2719)1011101
|k Patient Studies (Bonn)
|l Patient Studies (Bonn)
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1011201
980 _ _ |a I:(DE-2719)1011101
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21