% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Andersen:282580,
      author       = {Andersen, Olav M and de Waal, Matthijs W J and Monti,
                      Giulia and Tesi, Niccolo and Jensen, Anne Mette G and de
                      Geus, Christa and van Spaendonk, Rosalina and Vogel, Maartje
                      and Ahmad, Shahzad and Amin, Najaf and Amouyel, Philippe and
                      Beecham, Gary W and Bellenguez, Céline and Berr, Claudine
                      and Bis, Joshua C and Boland, Anne and Bossù, Paola and
                      Bouwman, Femke and Bras, Jose and Charbonnier, Camille and
                      Clarimon, Jordi and Cruchaga, Carlos and Daniele, Antonio
                      and Dartigues, Jean-François and Debette, Stéphanie and
                      Deleuze, Jean-François and Denning, Nicola and DeStefano,
                      Anita L and Dols-Icardo, Oriol and van Duijn, Cornelia M and
                      Farrer, Lindsay A and Fernández, Maria Victoria and van der
                      Flier, Wiesje M and Fox, Nick C and Galimberti, Daniela and
                      Genin, Emmanuelle and Gille, Johan J P and Grenier-Boley,
                      Benjamin and Grozeva, Detelina and Guen, Yann Le and
                      Guerreiro, Rita and Haines, Jonathan L and Holmes, Clive and
                      Hummerich, Holger and Arfan Ikram, M. and Kamran Ikram, M.
                      and Kawalia, Amit and Kraaij, Robert and Lambert,
                      Jean-Charles and Lathrop, Marc and Lemstra, Afina W and
                      Lleó, Alberto and Myers, Richard M and Mannens, Marcel M A
                      M and Marshall, Rachel and Martin, Eden R and Masullo, Carlo
                      and Mayeux, Richard and Mead, Simon and Mecocci, Patrizia
                      and Meggy, Alun and Mol, Merel O and Nacmias, Benedetta and
                      Naj, Adam C and Napolioni, Valerio and Nicholas Cochran, J.
                      and Nicolas, Gaël and Pasquier, Florence and Pastor, Pau
                      and Pericak-Vance, Margaret A and Pijnenburg, Yolande A L
                      and Piras, Fabrizio and Quenez, Olivier and Ramirez, Alfredo
                      and Raybould, Rachel and Redon, Richard and Reinders, Marcel
                      J T and Richard, Anne-Claire and Riedel-Heller, Steffi G and
                      Rivadeneira, Fernando and van Rooij, Jeroen G J and
                      Rousseau, Stéphane and Ryan, Natalie S and Sanchez-Juan,
                      Pascual and Schellenberg, Gerard D and Scheltens, Philip and
                      Schott, Jonathan M and Seshadri, Sudha and Sie, Daoud and
                      Sims, Rebecca and Sistermans, Erik A and Sorbi, Sandro and
                      van Swieten, John C and Tijms, Betty and Uitterlinden,
                      André G and Visser, Pieter Jelle and Wagner, Michael and
                      Wallon, David and Wang, Li-San and Williams, Julie and
                      Yokoyama, Jennifer S and Zarea, Aline and van der Lee, Sven
                      J and Olsen, Johan G and Hulsman, Marc and Holstege, Henne},
      title        = {{D}omain mapping of disease mutations reveals pathogenic
                      {SORL}1 variants in {A}lzheimer's disease.},
      journal      = {Molecular neurodegeneration},
      volume       = {20},
      number       = {1},
      issn         = {1750-1326},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DZNE-2025-01340},
      pages        = {122},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Age at onset (Other) / Alzforum mutation database (Other) /
                      Alzheimer’s disease (Other) / Disease risk (Other) /
                      Domain-mapping disease-mutations (Other) / Genetics (Other)
                      / Penetrance (Other) / Rare variants (Other) / SORL1 (Other)
                      / SORLA (Other)},
      cin          = {AG Wagner / Patient Studies (Bonn)},
      ddc          = {570},
      cid          = {I:(DE-2719)1011201 / I:(DE-2719)1011101},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41327266},
      pmc          = {pmc:PMC12667055},
      doi          = {10.1186/s13024-025-00907-z},
      url          = {https://pub.dzne.de/record/282580},
}