Citations 5
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Guen, Yann Le , Luo, Guo , Damotte, Vincent , Jansen, Iris E. , Nicolas, Aude , Rojas, Itziar de, Bellenguez, Céline , Lian, Michelle Mulan , Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier‐Boley, Benjamin , Naito, Tatsuhiko , Talyansky, Seth D., Yogeshwar, Selina , Sempere, Vicente Peris, Satake, Wataru , Álvarez, Victoria , Arosio, Beatrice , Boland, Anne , Daniele, Antonio , Darling, D.H., Dichgans, Martin , Dufouil, Carole , Düzel, Emrah , García‐Ribas, Guillermo, García‐Alberca, José María , García-González, Pablo, Giedraitis, Vilmantas , Graff, Caroline , Grünblatt, Edna , Hausner, Lucrezia , Jung, Yoo Jin , Deckert, Jürgen, Kern, Silke , Kuulasmaa, Teemu , Lee, Kun Ho , Lin, Ling , Masullo, Carlo , Mehrabian, Shima , Mendonça, Alexandre de , Boada, Merçé , Mir, Pablo , Moreno, Fermín , Nicolas, Gaël , Niida, Shumpei , Nordestgaard, Børge G. , Papenberg, Goran, Papma, Janne M., Pástor, Pau , Peters, Oliver , Popp, Julius , Molina‐Porcel, Laura , Puerta, Raquel , Pérez‐Tur, Jordi , Ramakers, Inez H.G.B. , Real, Luís Miguel , Riedel‐Heller, Steffi G. , Rodríguez‐Rodríguez, Eloy , Ross, Owen A. , Scarmeas, Nikolaos , Schneider, Anja , Solfrizzi, Vincenzo , Spalletta, Gianfranco , Tan, Eng‐King , Tegos, Thomas, Thomassen, Jesper Qvist , Tremolizzo, Lucio , Verhey, Frans, EADB, group, GR@ACE study, DemGene, EADI, GERAD, Blennow, Kaj , He, Zihuai , Jessen, Frank , Kehoe, Patrick G. , Duin, Cornelia van, Sánchez‐Juan, Pascual , Zettergren, Anna , Okada, Yukinori , Rossi, Giacomina, Gim, Jungsoo , Sims, Rebecca, Ramı́rez, Alfredo , Lambert, Jean‐Charles , Greicius, Michael D. , Mignot, Emmanuel , Moreno–Grau, Sonia , Rojas, Itziar de, Prokic, Ivana, Aarsland, Dag, García‐González, Pablo , Abdelnour, Carla , Armstrong, Nicola J. , Anthoula, Tsolaki, Archetti, Silvana, Pastor, Alfonso Arias, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa , Baquero, Miquel , Pastor, Ana Belén , Besse, Céline , Bizarro, Alessandra, Blesa, Rafael , Bossù, Paola , Brusco, Luis Ignacio , Buiza‐Rueda, Dolores, Bürger, Katharina , Burholt, Vanessa, Cecchetti, Roberta, Chillotti, Caterina , Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher , Costantini, Emanuele Maria , Daian, Delphine , Dartigues, Jean‐François, Escott-Price, Valentina, Ewers, Michael , Fernández‐Fuertes, Marta , Ferreira, Catarina B. , Fin, Bertrand, Fließbach, Klaus , Franco-Macías, Emlio, García-González, Pablo, García‐Madrona, Sebastián, Giegling, Ina, Giorgio, Giaccone, González-Pérez, Antonio, Grande, Giulia , Green, Emma , Grimmer, Timo, Hardy, John, Hartmann, Annette M. , Harwood, Janet , Helisalmi, Seppo , Hernández, Isabel, Hoffmann, Per, Vilas, Raquel Huerto, Hulsman, Marc , Johansson, Charlotte , Kilander, Lena, Ståhlbom, Anne Kinhult, Koivisto, Anne M. , Lage, Carmen , Lerch, Ondřej , Munain, Adolfo Lopez de, Löwemark, Malin, Luckcuck, Lauren, Maier, Wolfgang, Marco, Spallazzi, Montes, Ángel Martín, Rodríguez, Carmen Martínez, Meggy, Alun, Mendoza, Silvia, Moebus, Susanne, Morelli, Laura , Möthen, Markus M., Muchnik, Carolina , Orsini, Michela, Péricard, Pierre , Piñol-Ripoll, Gerard, Polak, Thomas, Quenez, Olivier , Rábano, Alberto , Ramakers, Inez, Riederer, Peter, Rongve, Arvid, Allende, Irene Rosas, Rujescu, Dan, Sakka, Paraskevi , Sánchez‐Arjona, María Bernal, Sando, Sigrid Botne , Scamosci, Michela, Scherbaum, Norbert, Scherer, Martin, Schott, Jonathan M., Shadrin, Alexey A, Skrobot, Olivia Anna, Solfrizzi, Vincenzo, Spottke, Annika , Stordal, Eystein , Tartan, Juan Pablo, Traykov, Latchezar , Tybjærg‐Hansen, Anne, Ullgren, Abbe, Ulstein, Ingun, Dongen, Jasper Van , Wallon, David, Windle, Gill, Woods, Bob , Zulaica, Miren , Laczó, Jan , Maťoška, Václav , Piras, Federica, Ciullo, Valentina , Shofany, Jacob, Andreoni, Simona, Zompo, Maria Del, Bastiani, Patrizia, Natunen, Teemu , Antikaínen, Riitta , Abraham, Richard, Al-Chalabi, Ammar, Brayne, Carol, Brown, Kristelle S., Collinge, John, Craig, David W. , Deloukas, Pangiotis, Gerrish, Amy, Gwilliam, Rhian, Hardy, John , Hollingworth, Paul, Johnston, Jarret A., Jones, Lesley , Lawlor, Brian, Lynch, Aoibhinn, McQuillin, Andrew, Owen, Michael J., Passmore, Peter , Proitsi, Petra, Rossor, Martin, Gurling, Hugh, Todd, Stephen, Mummery, Catherine J. , Ryan, Nathalie, Lacidogna, Giordano , Adarmes-Gómez, Ad, Mauleón, Ana , Pancho, Ana, Gailhajenet, A., Lafuente, Asunción, Martín, Elvira, Pelejà, Esther, Carrillo, F, Merlín, Isabel Sastre, Garrote-Espina, L. , Carrión‐Claro, Mario, Marín, María Esmeralda Arreola , Labrador, Ma, Buendía, Mar, Guitart, Marina, Moreno, Mariona, Ibarria, Marta, Periñán, Mt, Aguilera, Núria , Gómez-Garre, P, Escuela, R, Pineda-Sanchez, R., Vigo-Ortega, R, Preckler, Sílvia , Rodrigo‐Herrero, Silvia , Diego, Susana, Salvadori, Nicola, Chipi, Elena , Laske, Christoph , Janowitz, Daniel , Anastasiou, Anna, Parveen, Kayenat, López‐García, Sara , Antonell, Anna , Belezhanska, Diyana , Solís, Patricia , Medel, Nancy , Lisso, Julieta, Sevillano, Zulma, Politis, Daniel Gustavo , Cores, Valeria, Cuesta, Carolina , Ortíz, Cecilia, Bacha, Juan Ignacio, Rios, Mario, Saenz, Aldo, Abalos, Mariana Sanchez, Köhler, Eduardo, Palacio, Dana Lis, Etchepareborda, Ignacio, Prestia, Federico Ariel, Galeano, Pablo , Castaño, Eduardo M., Germani, Sandra, Toso, Carlos Reyes, Rojo, Matias, Ingino, Carlos A. , Mangone, Carlos A., Engelborghs, Sebastiaan , Nielsen, Sune Fallgaard, Farotti, Lucia , Biessels, Geert Jan , Fiévet, Nathalie, Forsell, Charlotte , Thonberg, Håkan, Bjerke, Maria , Roeck, Ellen De , Olivar, Natividad , Sachdev, Perminder S. , Magda, Tsolaki, Rossi, Giacomina, Andreassen, Ole A., Sims, Rebecca , Aguilera, N., Alarcón, Estefanía Burgos, Buendia, Marie‐Annick , Rojas, Itziar de , Diego, S. , Guitart, M., González-Péerez, A, Lafuente, A., Martin, Elisabeth , Martinez, M.T.M., Marquié, M, Olivé, C. , Pelejà, E., Puerta, R, Sáez, ME, Táarraga, L, Valero, S, Alonso, MD, Amer-Ferrer, G., Antequera, M., Antúnez, Carmen , Bernal, M. , Bullido, MJ, Ja, Burguera, Carrillo, F, Casajeros, MJ, Cruz-Gamero, JM, Escuela, R, Franco, Emilio, García-Alberca, JM, Madrona, S. García, Gómez-Garre, P, Hevilla, S., Espinosa, MA Labrador, Legaz, A. , Lleóo, A, Munáin, A Lóopez de, Marín-Muñoz, Juan, Marín, T, Marquié, M, Martínez, B. , Álvarez, A Martínez-Lage, Iriarte, M Mendioroz, Tur, J Péerez, Ripoll, G. Piñol, Ráabano, A, Asúa, Diego Real de , Rodrigo, S., Royo, JL, Díaz, R. Sanchez del Valle, Sánchez‐Juan, Pascual, Sastre, Isabel , Valero, S, Vicente, MP, Vigo-Ortega, R, Shadrin, Alexey A, Rongve, Arvid, Bosnes, Ingunn , Athanasiu, Lavinia, Aarsland, Dag, Andreassen, Ole A., Epelbaum, Jacques, Wallon, David, Hannequin, Didier , Campion, Dominique , Dermecourt, Vincent, Dubois, Bruno , Amouyel, Phillippe, Sims, Rebecca, Gerrish, Amy, Thomas, Charlene , Meggy, Alun, Davies, Chloe, Dowzell, Kimberley, Bernardo-Harrington, Mateus, Hoffmann, Per, Brown, Kristelle, Schott, Jonathan M., Rossor, Martin, Ryan, Natalie S. , Uphill, James, Al-Chalabi, Ammar, Bass, Nick, Abraham, Richard, Kölsch, Heike, Schürmann, Britta, Lacour, ndré, Herold, Christine, Johnston, Janet, Todd, Stephen, Proitsi, Petra, Patel, Yogen, Warden, Donald, Wilcock, Gordon , Clarke, Robert , Lawlor, Brian, McQuillin, Andrew, Hardy, John, Brayne, Carol, Deloukas, Panagiotis, Sussams, Rebecca, Warner, Nick, Bayer, Anthony, Singleton, Andrew, Rujescu, Dan, Giegling, Ina, Klopp, Norman, Mayhaus, Manuel, Riemenschneider, Matthias, Pinchler, Sabrina, Feulner, Thomas, Bussche, Hendrik den, Scherer, Martin, Hüll, Michael, Frölich, Lutz, Wichmann, H‐Erich, Jöckel, Karl‐Heinz , Moebus, Susanne, Kauwe, John, Mayo, Kevin H. , Escott-Price, Valentina, Peng, Rong , Tan, Louis, Tandiono, Moses , Ng, Ebonne, Prakash, Kumar‐M., Au, Wing‐Lok , Meah, Wee-Yang, Mok, Shi Qi, Chan, Anne , Chen, Ling , Jeon, Beom S., Lin, Juei‐Jueng , Pei, Zhong , Shi, Changhe , Song, Kyuyoung, Wu, Yih‐Ru , Xu, Yuming , Yan, Yaping , Yang, Jing , Zhang, Bao Rong, Le Guen, Yann , Damotte, Vincent , During, Emmanuel , Hort, Jakub , Lin, Ling , Niida, Shumpei , Pasquier, Florence , Real, Luis M , Rujescu, Dan , Spalletta, Gianfranco , Zetterberg, Henrik , Andreassen, Ole A , Tsolaki, Magda , Foo, Jia Nee , Mignot, Emmanuel , Dichgans, Martin , Ramirez, Alfredo , Ross, Owen A , Sachdev, Perminder S , Hardy, John , Nicolas, Gaël , Alvarez, Victoria , Mir, Pablo , Pastor, Pau , Boada, Merce , García-González, Pablo , Molina-Porcel, Laura , de Mendonça, Alexandre , Graff, Caroline , Ambati, Aditya , Yu, Eric , Rojas, Itziar de, Leal, Thiago Peixoto , Miyashita, Akinori , Küçükali, Fahri , Belloy, Michaël E. , Benussi, Luisa , Borroni, Barbara , Bullido, María J. , Caffarra, Paolo , Clarimón, Jordi , Darling, Daniel, Debette, Stéphanie , Deleuze, Jean‐François , Galimberti, Daniela , García-González, Pablo, Goldhardt, Oliver , Hanon, Olivier , Heilmann‐Heimbach, Stefanie , Holstege, Henne H. , Hort, Jakub , Mecocci, Patrizia , Moebus, Susanne , Nacmias, Benedetta , Parnetti, Lucilla , Pasquier, Florence , Pijnenburg, Yolande A.L. , Piñol‐Ripoll, Gerard , Rainero, Innocenzo , Royo, José Luís , Scheltens, Philip , Scherbaum, Norbert , Seripa, Davide , Skoog, Ingmar , Squassina, Alessio , Swieten, John C. van , Sánchez‐Valle, Raquel , Teunissen, Charlotte E. , Vyhnálek, Martin , Wærn, Margda , Wiltfang, Jens , Zhang, Jing , EADB, group, GR@ACE study, DemGene, EADI, GERAD, Zetterberg, Henrik , Williams, Julie , Amouyel, Philippe , Tsolaki, Magda , Frikke-Schmidt, Ruth , Sleegers, Kristel , Toda, Tatsushi , Ingelsson, Martin , Rossi, Giacomina, Hiltunen, Mikko O. , Ozaki, Kouichi , Sims, Rebecca, Foo, Jia Nee , Flier, Wiesje M. van der , Ikeuchi, Takeshi , Mata, Ignácio F. , Ruiz, Agustı́n , Gan‐Or, Ziv , Andrade, Víctor , Amin, Najaf , Campos-Martín, Rafael , Holmans, Peter , Kleineidam, Luca , Lee, Sven J. van der , Rojas, Itziar de, Yaqub, Amber , Prokic, Ivana, Costa, Marcos R. , Chapuis, Julien , Ahmad, Shahzad , Aarsland, Dag, Alarcón‐Martín, Emilio , Alcolea, Daniel , Alegret, Montserrat , Álvarez, Ignacio , Appollonio, Ildebrando Marco , Arcaro, Marina , Athanasiu, Lavinia, Berr, Claudine , Bessi, Valentina , Binetti, Giuliano , Boschi, Silvia , Bråthen, Geir , Bresner, Catherine , Brodaty, Henry , Brookes, Keeley J. , Burholt, Vanessa, Calero, Miguel , Chêne, Geneviève , Carracedo, Ãngel , Cervera‐Carles, Laura , Charbonnier, Camille , Claassen, Jurgen A.H.R. , Conti, Elisa , Corma‐Gómez, Anaïs , Custodero, Carlo , Dalmasso, Carolina , Dardiotis, Efthimios , Deyn, Peter Paul De , Ser, Teodoro del , Denning, Nicola , Diehl‐Schmid, Janine , Díez-Fairén, Mónica , Rossi, Paolo Dionigi , Djurovic, Srdjan , Duron, Emmanuelle , Escott-Price, Valentina, Espinosa, Ana , Ferri, Evelyn , Fischer, Peter A. , Fladby, Tormod , Fortea, Juan , Fostinelli, Silvia , Fox, Nick C. , Frank, Ana , Froelich, Lutz , García-González, Pablo, Ghidoni, Roberta , Giegling, Ina, Grimmer, Timo , Guetta‐Baranes, Tamar , Haapasalo, Annakaisa , Hadjigeorgiou, Georgios M. , Hampel, Harald , Hardy, John, Heneka, Michael T. , Hernández, Isabel, Herrmann, Martin J. , Hoffmann, Per, Holmes, Clive , Kivipelto, Miia , Kornhuber, Johannes , Kosmidis, Mary H. , Laukka, Erika J. , Lauria, Alessandra , Lehtisalo, Jenni , Lleó, Alberto , Munain, Adolfo Lopez de, Macías, Juan, MacLeod, Catherine Anne , Mangialasche, Francesca , Marquié, Marta , Marshall, Iain James , Mead, Simon , Medina, Miguel , Meggy, Alun, Menéndez‐González, Manuel , Moebus, Susanne, Mol, Merel O. , Montrreal, Laura , Morgan, Kevin , Ngandu, Tiia , Olaso, Robert , Orellana, Adelina , Ortega, Gemma , Padovani, Alessandro , Pérez‐Cordón, Alba , Pineda, Juan Antonio , Piñol-Ripoll, Gerard, Pisanu, Claudia , Posthuma, Daniëlle , Priller, Josef , Quintela, Inés , Reinders, Marcel J. T. , Roberto, Natalia , Rongve, Arvid, Rosende‐Roca, Maitée , Rubino, Elisa , Rujescu, Dan, Sáez, María Eugenia , Saltvedt, Ingvild Tina , Sanabria, Ángela , Sánchez-García, Florentino , Scarpini, Elio , Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias C. , Schott, Jonathan M., Selbæk, Geir , Shadrin, Alexey A, Soininen, Hilkka S. , Solfrizzi, Vincenzo, Solomon, Alina , Sorbi, Sandro , Sotolongo‐Grau, Óscar , Tárraga, Lluís , Tesi, Niccoló , Thalamuthu, Anbupalam , Uitterlinden, André G. , Valero, Sergi , Lugt, Aad van der , Rooij, Jeroen van , Vandenberghe, Rik , Vidal, Jean‐Sébastien , Vogelgsang, Jonathan S. , Wagner, Michael , Wallon, David , Weinhold, Leonie , Yannakoulia, Mary , Serpente, María , Assogna, Francesca , Piras, Fabrizio , Piras, Federica, Ferrarese, Carlo , Sala, Gessica , Zoia, C , Benussi, Alberto , Takalo, Mari , Laatikainen, Tiina K. , Tuomi, Tiinamaija , Strandberg, Timo E. , Lindström, Jaana , Peltonen, Markku , Abraham, Richard, Al-Chalabi, Ammar, Bass, Nicholas , Brayne, Carol, Gerrish, Amy, Gill, Michael , Harold, Denise , Lawlor, Brian, Livingston, Gill , Lovestone, Simon , Lupton, Michelle K. , Mann, David , McGuinness, Bernadette , McQuillin, Andrew, O‘Donovan, Michael , Powell, John , Proitsi, Petra, Rossor, Martin, Shaw, Christopher E. , Smith, A. David , Todd, Stephen, Macías‐García, Daniel , Carrillo, F, Vargas, Liliana , Marín, M, Alonso, María Dolores, Gómez-Garre, P, Cañabate, Pilar , Escuela, R, Vigo-Ortega, R, Jesús, Silvia , Vacca, Alessandro , Roveta, Fausto , Boecker, Henning , Perneczky, Robert , Anastasiou, Costas Anastasios , Malik, Rainer , Parveen, Kayenat, Mihova, Kalina Yonkova , Weber, Heike , Kochen, Silvia , Saenz, Aldo, Kohler, Matias, Novack, Gisela Vanina , Tagliavini, Fabrizio , Nielsen, Sune Fallgaard, Fenoglio, Chiara , Biessels, Geert Jan , Love, Seth , Broeckhoven, Christine Van , Rubinsztein, David Chaim , Teipel, Stefan Johannes , Deramecourt, Vincent , Martínez-Larrad, María Teresa, Ghanbari, Mohsen , Mather, Karen A. , Ikram, M. Arfan , Rossi, Giacomina, Andreassen, Ole A., Duijn, Cornelia M. van , Alarcon, E, Buendia, M, Cano, Amanda C. , Anchuelo, Arturo Corbatón , Macı́as, Juan , Maroñas, Olalla , Martín, E, Martínez, MT, Marquié, M, Moreno, M. , Núñez‐Llaves, Raúl , Olivé, C, Puerta, R, Serrano‐Ríos, Manuel , Valero, S, Bernal, M, Carrillo, F, Pancorbo, Marian M. de , Escuela, R, Gómez-Garre, P, Munaín, Adolfo López de , Manzanares, Salvadora , Marín, M, Marquié, M, Martínez, B, Martínez, C, Martínez, V, Álvarez, A Martínez-Lage, Iriarte, M Mendioroz, Tur, J. Pérez, Periñán, María Teresa , Rodrigo, S, Valero, S, Vigo-Ortega, R, Vivancos, L. , Shadrin, Alexey A, Bahrami, Shahram , Rongve, Arvid, Athanasiu, Lavinia, Selnes, Per , Bergh, Sverre , Aarsland, Dag, Andreassen, Ole A., Tzourio, Christophe , Brice, Alexis , Ritchie, Karen , Sims, Rebecca, Gerrish, Amy, Williams, Amy, Meggy, Alun, Nash, William, Castillo-Morales, Atahualpa , Hoffmann, Per, Turton, James , Lord, Jenny , Vardy, Emma , Fisher, Elizabeth , Warren, Jason D. , Schott, Jonathan M., Rossor, Martin, Guerreiro, Rita , Al-Chalabi, Ammar, Bass, Nick, Abraham, Richard, Heun, Reinhard , Todd, Stephen, Proitsi, Petra, Hodges, Angela , Becker, Tim , Lawlor, Brian, McQuillin, Andrew, Hardy, John, Brayne, Carol, Deloukas, Panagiotis, Ben‐Shlomo, Yoav , Hooper, Nigel M. , Pickering‐Brown, Stuart , Warner, Nick, Bayer, Anthony, Singleton, Andrew , Rujescu, Dan, Giegling, Ina, Heuser, Isabella , Drichel, Dmitriy , Nöthen, Markus M. , Riemenschneider, Matthias, Gu, Wei , Scherer, Martin, Moebus, Susanne, Morris, John C. , Owen, Michael J. , Escott-Price, Valentina, Chew, Elaine Guo Yan , Chung, Sun Ju , Chao, Yinxia , Ahmad‐Annuar, Azlina , Chen, Yongping , Jiang, Lulu , Lim, Jia Lun , Liu, Chun‐Feng , Mao, Chengjie , Mok, Vincent , Pei, Zhong , Shang, Huifang , Tan, Ai Huey , Xu, Renshi , Zhang, Bao Rong, Koh, Woon‐Puay , Lim, Shen‐Yang , Khor, Chiea Chuen , Liu, Jianjun
Proceedings of the National Academy of Sciences | August 29, 2023 | Volume: 120 | Issue: 36 | Pages: No page available
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
Vascular dysfunction—The disregarded partner of Alzheimer's disease
Sweeney, Melanie D. , Montagne, Axel , Nation, Daniel A. , Schneider, Lon S. , Chui, Helena C., Harrington, Michael G. , Pa, Judy , Law, Meng , Wang, Danny J.J. , Jacobs, Russell E. , Doubal, Fergus , Ramirez, Joel , Dichgans, Martin , Love, Seth , Bath, Philip M. , Markus, Hugh S. , Salman, Rustam Al‐Shahi , Kalaria, Rajesh N., Werring, David J. , Moskowitz, Michael A., Katušić, Zvonimir S. , Lazarov, Orly , Rehman, Jalees , Wellington, Cheryl L. , González, Héctor M. , Yuan, Chun , Lockhart, Samuel N. , Hughes, Timothy M. , Chen, Christopher , Sachdev, Perminder S. , O’Brien, John T. , Pantoni, Leonardo , Gustafson, Deborah , Biessels, Geert Jan , Wallin, Anders , Wong, Adrian , Passmore, Peter , Barkof, Frederick, Muller, Majon , Román, Gustavo C. , Hamel, Édith , Seshadri, Sudha , Buchem, Mark A. van , Arvanitakis, Zoe , Drewes, Lester R. , Hachinski, Vladimir , Wardlaw, Joanna M. , Kalaria, Raj N. , Dichgans, Martin , O'Brien, John Tiernan , Wardlaw, Joanna Marguerite , Seshadri, Sudha , Sachdev, Perminder S , Sagare, Abhay P. , Chui, Helena C. , Black, Sandra E. , Nedergaard, Maiken , Benveniste, Helene , Iadecola, Costantino , Allan, Stuart McRae , Quinn, Terence J , Carare, Roxana Octavia , Touyz, Rhian M. , Williams, Steven , Lutz, Sarah E. , Minshall, Richard D. , Davis, Thomas P. , Gonzalez, Hector M , Skoog, Ingmar , Biessels, Geert Jan , Smith, Eric Edward , Mok, Vincent , Breteler, Monique M.B. , Gottesman, Rebecca F. , Schneider, Julie A. , Finch, Caleb E. , Toga, Arthur W. , Zloković, Berislav V. , Al-Shahi Salman, Rustam , Werring, David John , Wang, Danny J J
Alzheimer's & Dementia | January 11, 2019 | Volume: 15 | Issue: 1 | Pages: 158-167
Abstract Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.
The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
Gerrish, Amy , Russo, Giancarlo , Richards, Alexander , Moskvina, Valentina, Ivanov, Dobril , Harold, Denise , Sims, Rebecca , Abraham, Richard, Hollingworth, Paul, Chapman, Jade , Hamshere, Marian L. , Pahwa, Jaspreet Singh, Dowzell, Kimberley, Jones, Nicola, Thomas, Charlene , Stretton, Alexandra, Morgan, Angharad R., Lovestone, Simon , Powell, John , Proitsi, Petroula , Brayne, Carol , Gill, Michael , Lynch, Aoibhinn, Morgan, Kevin , Brown, Kristelle, Passmore, Peter , Craig, David W. , McGuinness, Bernadette , Todd, Stephen , Johnston, Janet, Smith, A. David , Love, Seth , Kehoe, Patrick G. , Hardy, John , Mead, Simon , Fox, Nick C. , Rossor, Martin N. , Collinge, John, Maier, Wolfgang, Jessen, Frank , Kölsch, Heike, Schürmann, Britta, Bussche, Hendrik van den, Heuser, Isabella , Kornhuber, Johannes , Wiltfang, Jens , Dichgans, Martin , Frölich, Lutz, Hampel, Harald , Hüll, Michael, Goate, Alison , Kauwe, John, Cruchaga, Carlos , Nowotny, Petra, Morris, John C. , Mayo, Kevin H. , Livingston, Gill , Gurling, Hugh, McQuillin, Andrew , Gwilliam, Rhian, Deloukas, Panagiotis, Davies, Gail , Starr, John M. , Deary, Ian J. , Al‐Chalabi, Ammar , Shaw, Christopher E. , Tsolaki, Magda , Singleton, Andrew B., Guerreiro, Rita , Mühleisen, Thomas W. , Nöthen, Markus M. , Moebus, Susanne , Jöckel, Karl‐Heinz , Klopp, Norman, Wichmann, H‐Erich, Carrasquillo, Minerva M., Younkin, Steven G., Jones, Lesley , Holmans, Peter , O‘Donovan, Michael , Williams, Julie , Deloukas, Panos , Escott‐Price, Valentina , Denning, Nicola , Dichgans, Martin , Cruchaga, Carlos , Kornhuber, Johannes , Nöthen, Markus M , Hardy, John , Moebus, Susanne , Williams, Amy L. , Lupton, Michelle K. , Rubinsztein, David Chaim , LAWLOR, BRIAN A. , Holmes, Clive , Mann, David , Heun, Reinhard , Rujescu, Dan , Bass, Nicholas , Harris, Sarah , Carrasquillo, Minerva M. , Pankratz, V. Shane , Owen, Michael J. , Fox, Nick C , Morris, John C , Wiltfang, Jens , Al-Chalabi, Ammar , Tsolaki, Magda , Goate, Alison M , McQuillin, Andrew , Escott-Price, Valentina
Journal of Alzheimer's Disease | May 16, 2018 | Volume: 28 | Issue: 2 | Pages: 377-387
A Multi-Center Study of ACE and the Risk of Late-Onset Alzheimer's Disease
Belbin, Olivia , Brown, Kristelle, Shi, Hui , Medway, Christopher, Abraham, Richard, Passmore, Peter , Mann, David, Smith, A. David , McGuinness, Bernadette , Craig, David , Warden, Donald, Kölsch, Heike, Love, Seth , Kalsheker, Noor , Williams, Julie , Carrasquillo, Minerva M., Younkin, Steven G., Morgan, Kevin , Kehoe, Patrick G. , Belbin, Olivia , Mann, David, Holmes, Clive , Heun, Reinhard , Owen, Michael J. , Carrasquillo, Minerva M.
Journal of Alzheimer's Disease | May 16, 2018 | Volume: 24 | Issue: 3 | Pages: 587-597
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Jones, Lesley , Lambert, Jean‐Charles , Choi, Seung‐Hoan, Harold, Denise , Vedernikov, Alexey , Escott‐Price, Valentina , Stone, Timothy, Richards, Alexander , Bellenguez, Céline , Sims, Rebecca , DeStefano, Anita L. , Bis, Joshua C. , Beecham, Gary W. , Grenier‐Boley, Benjamin , Russo, Giancarlo , Thornton‐Wells, Tricia A., Jones, Nicola, Smith, Albert V. , Thomas, Charlene , Zélénika, Diana, Kamatani, Yoichiro, Lin, Chiao‐Feng , Schmidt, Helena , Kunkle, Brian W. , Dunstan, Melanie , Ruiz, Agustı́n , Bihoreau, Marie‐Thérèse, Reitz, Christiane, Hollingworth, Paul, Hanon, Olivier , Fitzpatrick, Annette L., Buxbaum, Joseph D. , Campion, Dominique , Crane, Paul K. , Guðnason, Vilmundur , Cruchaga, Carlos , Craig, David W. , Amin, Najaf , Jager, Philip L. De , Deramecourt, Vincent , Johnston, Janet, Evans, Denis A., Lovestone, Simon , Letteneur, Luc, Kornhuber, Johanes, Tárraga, Lluís , Eiriksdottir, Gudny, Goate, Alison , Fiévet, Nathalie, Huentelman, Matthew J. , Gill, Michael , Emilsson, Valur , Brown, Kristelle, Kamboh, M. Ilyas , Keller, Lina, Barberger‐Gateau, Pascale, McGuinness, Bernadette , Larson, Eric B., Dufouil, Carole , Todd, Stephen , Wallon, David , Kehoe, Patrick G. , George‐Hyslop, Peter St , Lleὀ, Alberti, Bayer, Anthony, Tsuang, Debby W. , Yu, Lei, Tsolaki, Magda , Bossù, Paola , Spalletta, Gianfranco , Proitsi, Petra, Collinge, John, Sorbi, Sandro , Hardy, John , Naranjo, María Cándida Déniz, Razquín, Cristina , Bosco, Paola , Clarke, Robert , Brayne, Carol , Galimberti, Daniela , CFAS, MRC, Moebus, Susanne , Mecocci, Patrizia , Zompo, Maria Del, Maier, Wolfgang, Hampel, Harald , Pilotto, Alberto, Bullido, María J. , Panza, Francesco , Caffarra, Paolo , Nacmias, Benedetta , Gilbert, John R., Mayhaus, Manuel, Jessen, Frank , Dichgans, Martin , Lannfelt, Lars , Håkonarson, Håkon , Pichler, Sabrina, Carrasquillo, Minerva M., Beekly, Duane, Alavarez, Victoria, Zou, Fanggeng, Younkin, Steven G., Hamilton‐Nelson, Kara L., Mateo, Ignacio, Faber, Kelley M., Jónsson, Pálmi V. , Combarros, Onofre, O‘Donovan, Michael , Cantwell, Laura B., Blacker, Deborah , Mead, Simon , Harris, Tamara B., Fratiglioni, Laura , Bruijn, Renée F.A.G. de, Passmore, Peter , Montine, Thomas J. , Bettens, Karolien, Rotter, Jerome I. , Brice, Alexis , Morgan, Kevin , Foroud, Tatiana, Kukull, Walter A. , Hannequin, Didier , Powell, John , Nalls, Michael A., Ritchie, Karen , Lunetta, Kathryn L. , Kauwe, John S.K., Boerwinkle, Eric , Riemenschneider, Matthias, Boada, Merçé , Hiltunen, Mikko , Martin, Eden R. , Pástor, Pau , Schmidt, Reinhold, Dartigues, Jean‐François, Mayeux, Richard , Tzourio, Christophe , Hofman, Albert , Nöthen, Markus M. , Graff, Caroline , Haines, Jonathan L. , Lathrop, Mark, Pericak‐Vance, Margaret A. , Launer, Lenore J. , Farrer, Lindsay A. , Duijn, Cornelia M. van , Broeckhoven, Christine Van , Ramı́rez, Alfredo , Schellenberg, Gerard D., Seshadri, Sudha , Amouyel, Philippe , Williams, Julie , Holmans, Peter , Bennett, David A. , Proitsi, Petroula , Ballantyne, Christie M. , Denning, Nicola , Wang, Weixin , Ibrahim‐Verbaas, Carla A. , Naj, Adam Christian , Gerrish, Amy , Jun, Gyungah , Chouraki, Vincent Antoine , Ikram, M. Arfan , Vardarajan, Badri Narayan , Kamatani, Yoichiro, Pasquier, Florence , Becker, Tim , Cruchaga, Carlos , Berr, Claudine , López, Oscar L. , Rubinsztein, David Chaim , Sleegers, Kristel , Myers, Amanda , Love, Seth , Rogaeva, Ekaterina A. , Gallacher, John , Clarimón, Jordi , Bayer, Anthony, Proitsi, Petra, Sánchez-García, Florentino , Fox, Nick C. , Mancuso, Michelangelo , CFAS, MRC, Carrasquillo, Minerva M. , Ingelsson, Martin , Valladares, Otto , Coto, Eliécer , Hamilton‐Nelson, Kara L. , Owen, Michael J. , Soininen, Hilkka S. , Mosley, Thomas H. , Bennett, David , Holmes, Clive , Riemenschneider, Matthias, Rujescu, Dan , Psaty, Bruce M. , Bennett, David A. , Dichgans, Martin , Ramirez, Alfredo , Hakonarson, Hakon , Nöthen, Markus M , Seshadri, Sudha , Hardy, John , Amouyel, Philippe , Tzourio, Christophe , van Duijn, Cornelia M , Smith, Albert V , Ballantyne, Christie M , Rotter, Jerome I , Moebus, Susanne , Ruiz, Agustín , Pastor, Pau , Boada, Merce , Tsolaki, Magda , Brice, Alexis , Goate, Alison M , Galimberti, Daniela , Escott-Price, Valentina , Mecocci, Patrizia , Nacmias, Benedetta , Graff, Caroline , Riemenschneider, Markus J.
Alzheimer's & Dementia | December 20, 2014 | Volume: 11 | Issue: 6 | Pages: 658-671
AbstractBackgroundLate‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome‐ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.