Citations 3
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
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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.
Accelerating the Search for Interventions Aimed at Expanding the Health Span in Humans: The Role of Epidemiology
Kritchevsky, Stephen B. , Guralnik, Jack M. , Cummings, Steven R. , Salive, Marcel E. , Kuchel, George A. , Schrack, Jennifer A. , Morris, Martha Clare , Weir, David R. , Ben‐Shlomo, Yoav , Kirkland, James L. , Ferrucci, Luigi , Kirkland, James, Ferrucci, Luigi , Kritchevsky, Stephen B , Kuchel, George A , Newman, Anne B. , Baccarelli, Andrea , Murabito, Joanne M. , Espeland, Mark Andrew , Melzer, David R.
The Journals of Gerontology: Series A | November 13, 2019 | Volume: 75 | Issue: 1 | Pages: 77-86
Abstract Background Extensive work in basic and clinical science suggests that biological mechanisms of aging are causally related to the development of disease and disability in late life. Modulation of the biological mechanisms of aging can extend both life span and health span in animal models, but translation to humans has been slow. Methods Summary of workshop proceedings from the 2018–2019 Epidemiology of Aging Workshop hosted by the Intramural Research Program at the National Institute on Aging. Results Epidemiologic studies play a vital role to progress in this field, particularly in evaluating new risk factors and measures of biologic aging that may influence health span, as well as developing relevant outcome measures that are robust and relevant for older individuals. Conclusions Appropriately designed epidemiological studies are needed to identify targets for intervention and to inform study design and sample size estimates for future clinical trials designed to promote health span.
Bone Research Society Abstracts
Team, the ERC ADREEM, Roelofs, Anke J. , Cummings, Steven R. , Bhimjiyani, A. , Neuburger, Jenny , Gregson, Celia L, Sparkes, Penny C. , Swiatkowska, Agnes, Lelliott, Christopher J. , Williams, Graham R. , Bassett, J. H. Duncan , Paton‐Hough, Julia, Tazzyman, Simon , Evans, Holly , Lath, Darren , Down, Jenny , Green, Alanna, Snowden, John A. , Chantry, Andrew, Na, Harvey, Shepstone, Lee , Kanis, John А. , Lenaghan, Elizabeth, Clarke, Shane, Harvey, I., Heawood, Ali, Howe, Amanda , Marshall, Tarnya, McCloskey, Eugène , Group, the SCOOP Trial, Hardy, Rebecca , Adams, Judith E., Aspden, Richard, Js, Gregory , Vlachopoulo, Dimitris, Maslin, Kate , Gossiel, Fatma , Bishop, Nicholas , Fraser, Robert, Gandhi, Saurabh , Prentice, Ann , Schoenmakers, Inez , Eastell, Richard , Cooper, Cyrus, Group, the MAVIDOS Trial, Ward, Kate, Cooper, Cyrus, Dennison, Elaine, Bonnet, Cleo, Eccles, Emily, Norman, K. Duane, Ko, Jeong‐Hun, Williams, G. Rhys, Madhusudan, Namrata, Bountra, C. , Oppermann, Udo , Oreffo, Richard OC , McEwan, Josephine, White, Kate L. , Oreffo, Richard, Dunlop, D. , Cornish, Jillian , Goring, Alice, Boyde, A. , Hesse, Eric , Olsen, Björn, Pitsilides, Andrew, Oreffo, Richard, Hartley, A M, Fraser, William, Tobias, JS, Harvey, Nicolas, Johansson, Helena , Cooper, Cyrus, Team, SCOOP Study, Roberts, Fiona , Rashdan, Nabil A. , Staines, Katherine, Milne, Elspeth , Morton, Nicholas M. , McCulloch, Kendal, Dunning, Lynette, Lockhart, John C. , Thomas, Neil Peter, Ranganath, L. , Gallagher, James A., Ward, Kate, Stewart, Angela, Garratt, Liz, Bastin, Sonja , Gamble, Gregory D., Shaw, Nick , Prieto-Alhambra, D, Cooper, Cyrus, Hughes, Juliette H. , Liu, Ke , Hughes, Andrew, Nijjar, Jagtar Singh , Padley, Jessica, Poole, Ken, Litwic, Anna, Dennison, Elaine, Edwards, Mark H. , Cooper, Cyrus, Dennison, Elaine, Ishimoto, Yuyu , Cooper, Cyrus, Ntani, Georgia , Yamada, H. , Muraki, Shigeyuki , Yoshida, Munehito , Yoshimura, Tan, Juan, Poole, Kenneth, Larrouture, Quitterie C. , Athanasou, Nick, Al-Sari, Usama , Felder, Alessandro , Chua, Melissa Y, Lodhia, Kalyani, Kłosowski, Michał M. , Farquharson, Colin, Inglis, Stefanie , Redl, Heinz , Oreffo, Richard, Gogakos, Apostolos , Ebri, Davide Komla, Pipelines, Sanger Mouse, Cidonio, Gianluca , Lanham, Stuart , Dawson, Jonathan, Oreffo, Richard, McEwan, Josephine, Wells, Julia, Oka, Hiroyuki , Iidaka, Toshiko , Kodama, Rie , Horii, Chiaki , Nakamura, Kozo, Akune, Toru, Hudson, Katie, Fisher, Matt , Chantry, Andrew, Adoum, Anne‐Tounsia, Bassett, Duncan, Mannan, Naila S., Dewhurst, Hannah F. , Ghirardello, Elena J. , Pipelines, Sangar Mouse, Komla‐Ebri, David, Curry, Katharine F., 𠀉, JH, Ganguly, Payal , Sparkes, Penny, Curry, Katherine F., Sim, Alisia, Kaczynski, Jakub , Novak, Amanda , Mills, David , Bonnet, Cleo, Ihenacho, Menna, Cronin, Rose‐Marie, Mason, Debbie , Rodriguez, Alexander, Xu, Cecilia, Scott, David , Dennison, Elaine, Stephenson, Sonya, Cosulich, Carlotta, Cooper, Cyrus, Sano, Hiroshige, Kondo, Naoki , Shimakura, Taketoshi, Fujisawa, Junichi, Kijima, Yasufumi, Skingle, Linda , Yamamoto, Noriaki , Takahashi, Hideaki E. , Endo, Naoto , Beamish, Rebecca, Evans, Sam, Morgan, Stephanie , Hooper, Kirsty M. , Halewood, Katherine , Stevens, Craig , Staines, Katherine, Steenhuis, Pieter, Ignelzi, Michael A., Morris, Michael D., Karabetsos, Matthew, VanRenterghem, Gloria, Ayyalusamy, Ramamoorthy, Kadamban, Premila, Vaughan‐Lane, Timothy, Wright, Maria da Glória Miotto , Poole, Kenneth , Cooper, Cyrus, Neven, Ellen, Wheeler‐Jones, Caroline , Rukuni, Ruramayi , Crabtree, Nicola , Mukwasi, Cynthia, McHugh, Grace , Gregson, Celia L, Luo, Jin , Dodhia, Vikash , Czekanska, Ewa M., Oreffo, Richard, Arnold, Emily L. , Gohin, Stéphanie , Soper, Robin, Ytrebø, Lars Marius , Meeson, Richard , Howat, D. , Hodges, Stephen , Evelyn‐Wright, Stephanie , Mavrogordato, Mark , Rankin, Kathryn , Stocks, Oliver, Hartley, Chris , Kerslake, R. W. , Thomson, Seamus , Muderis, Munjed Al, Ward, Kevin R. , Sowman, Aneka, Hart, Deborah , Spector, Tim D. , Coxon, Joshua, Townsend, Paul , Jones, Rebecca , Lawrence, Kevin M., Egan, B. T., Tattersall, Luke , Holm, Stefan H. , Martin, Jenny, Saunders, Fiona, Martin, J F, Saunders, Fiona, Davies, Amanda, Hugtenburg, R.P. , Wintsch, Emma, Anderson, Susan, Alshamrani, Hassan A. , Paggiosi, Margaret , Bishop, Nick , Offiah, Amaka C , Pretorius, Sarah, Roberts, Scott, Logan, Malcolm , Allaire, Brett , Bouxsein, Mary , Olatokun, Olamide, Nash, Thomas H., Abdul-Jabar, Hani B., Tran, Anh Nhi, Segeletz, Sandra, McDermott, Emma, Wileman, Tom, Helfrich, Miep , Redman, Amelia, Elford, Carole, Evans, Bronwen, Bradley, Mark , Martín, Iván , Khosla, Sundeep , Mahajan, Sumeet , Heller, Markus O.W. , Schneider, Philipp , Bonewald, Lynda F. , Lillycrop, Karen A. , Hanson, Mark, Lord, Janet M. , Maes, Christa , Ben‐Shlomo, Yoav , Leitch, Victoria D. , Logan, John G. , Croucher, Peter Ian , Lawson, Michelle Anne , Chantry, Andrew , Parsons, Camille M. , Fordham, Richard J , Gittoes, Neil , Holland, Richard , Redmond, Niamh Maria , Peters, T. J. , Torgerson, David John , O’Neill, Terence W , Cooper, Cyrus , Ireland, Alex , Muthuri, Stella G. , Saunders, Fiona R. , Pavlova, Anastasia Vladimirovna , Martin, Kathryn Remmes , Barr, Rebecca J. , Kuh, Diana J. , Cooper, Rachel , BARKER, ALAN ROBERT , Ubago‐Guisado, Esther , Williams, Craig Anthony , Gracia‐Marco, Luis , Curtis, Elizabeth Mary , D’Angelo, Stefania , Moon, Rebecca Jane , Crozier, Sarah , Kennedy, Stephen , Papageorghiou, Aris T. , Fraser, Robert, Inskip, Hazel M. , Godfrey, Keith M. , Javaid, M K , Cooper, Cyrus, Harvey, Nicholas C. , Group, the MAVIDOS Trial, Fuggle, Nicholas R. , Westbury, Leo D. , Syddall, Holly Emma , Ward, Kate, Duggal, Niharika Arora , Bonnet, Cleo Selina , Gilbert, Sophie J. , Norman, Kingsley, Mason, Deborah J. , Pereira, Marie , Petretto, Enrico , Williams, Graham R, Behmoaras, Jacques V. , Andrés, María C. de , Goriainov, Vitali , McEwan, Josephine K, White, Kate, Ferrara, Napoleone, Olsen, Bjorn, Clarkin, Claire E. , Paternoster, Lavinia , Kemp, John P. , Evans, David, TANG, JONATHAN C. Y. , Tobias, Jon H, Gregson, Celia Louise , Harvey, Nicolas, Orriss, Isabel R. , Ahmed, Faisal, Farquharson, Colin , MacRae, Vicky E. , Huesa, Carmen , Hof, Rob vanʼt , Goodyear, Carl S. , Thomas, Neil P. , Jeffery, Nathan S. , Breasail, Mícheál Ó , Reid, Ian R. , Horne, Anne M. , Mihov, Borislav , Bolland, Mark J , Delmestri, Antonella , Pinedo‐Villanueva, Rafael , Wilson, Peter, Hughes, Andrew, Bou–Gharios, George , Ward, Kate, Yamada, Hiroshi, Hashizume, Hiroshi , Tanaka, Sakae , Walker-Bone, Karen E , Knowles, Helen J. , Snelling, Sarah , Tobias, Jon H, Clark, Emma , Doube, Michael , Hutchinson, John R. , Shefelbine, Sandra J. , Dillon, Scott , Nudelman, Fabio , Kanczler, Janos M. , Schneider, Karl H. , Pollard, Andrea S. , Butterfield, Natalie C. , Williams, Graham R, Ahlfeld, Tilman , Glinka, Michael , Kim, Yang‐Hee , Yang, Shoufeng , Gelinsky, Michael , Wells, Julia A. , Kawaguchi, Hiroshi , Fisher, Matt, Miszkiewicz, Justyna Jolanta , Yoshimura, Takashi , Allen, Rebecca S. , El‐Jawhari, Jehan J. , Burska, Agata N. , Ponchel, Frédérique , Giannoudis, Peter Vasilios , Jones, Elena , Komla-Ebri, Davide S. K. , Hohenstein, Peter , Hung, John , Newby, David E. , Baker, Andrew, Karsenty, Gérard , Hsu, Shun‐Neng , Staines, Katherine Ann , Blain, Emma J. , Mason, Debbie, Rodriguez, Alexander, McMillan, Lachlan B. , Srikanth, Velandai , Ebeling, Peter R. , Javaheri, Behzâd , Ferrara, Napoleone, Olsen, Bjorn, Pitsillides, Andrew A. , Jones, Tim J , Clynes, Michael A. , James, Anthony , Harvey, Nicolas, Ersek, Adel , Cosulich, Carlotta Cecilia, Udalova, Irina A. , Horwood, Nicole J. , Jameson, Karen, Dennison, Elaine Margaret , Ayre, Wayne Nishio , Evans, Sam, Morgan, Stephanie, Mandair, Gurjit S. , Kohn, David H. , Kadamban, Premila, Galloway, James Benjamin , Vaughan-Lane, Tim, Wright, Maria, Brassett, Cecilia , Poole, Kenneth, Judge, Andrew , Leyland, Kirsten M. , Bourne, Lucie E. , Patel, Jessal J. , D’Haese, Patrick C. , Majonga, Edith D. , Mujuru, Hilda Angela , Ferrand, Rashida A. , Chen, Jiye , Dawson, Jonathan I. , Geng, Jin , Lim, Khoon S. , Woodfield, Tim B. F. , Greenwood, Charlene , Rogers, Keith D. , McGivern, Hannah , Márquez‐Grant, Nicholas , Zioupos, Peter , Hopkinson, Mark , Howat, David, Williams, Katherine A. , Gostling, Neil J. , Dyke, Gareth J. , Browne, Martin , Woods, Christopher, Dickinson, Alex , Zakrzewski, Sonia , Hartley, Chris, Folland, Jonathan P. , Brooke-Wavell, Katherine S. F. , Ossipov, Dmitri A. , Lu, William W. , Arden, Nigel , Edwards, James R., Kluzek, Stefan , Sanchez-Santos, Maria Teresa , Ismail, Omar Mohammad , Egan, Ben, Birchall, James C. , Heard, Charles, Marchi, Elena De , Virgilio, Francesco Di , Adinolfi, Elena , Gartland, Alison , Moura, Catarina Costa , Tare, Rahul S. , Xavier, Miguel , Beech, Jason Paul , Spencer, Daniel C. , Tegenfeldt, Jonas Olof , Morgan, Hywel , Murphy, Caitlin C. , Gregory, J.S. , Riemen, Anna H.K. , Davies, Amanda, Ahmad, Faizan , Theobald, Peter S. , Johnston, Richard, Piercy, Richard J. , Millar, Sophie , Anderson, Susan, O’Sullivan, Saoirse Elizabeth , Roberts, Scott, Jóhannesdóttir, Fjóla , Anderson, Dennis , Samelson, Elizabeth J , Kiel, Douglas P. , Nash, Thomas, Rochford, Justin J. , Al‐Sabah, Ayesha , Hardy, Rebecca
JBMR Plus | October 2, 2018 | Volume: 2 | Issue: S1 | Pages: No page available