10 research outputs found
Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of non-alcoholic fatty liver disease
- Author
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2013
- Field of study
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro CarĂ Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
- Anthony Alpha
- Antoine Marchalot
- Antoine Pierre
- Antoine Studer
- Anumakonda Vikram
- Aparicio Christelle
- Aquino Maia
- Arabi Yaseen M.
- Arachchige Malka
- Aravindan Latha
- Arbane Gill
- Archambault Patrick
- Archer Simon
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- Arnold John
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- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
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- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 nonâcritically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ supportâfree days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of non-alcoholic fatty liver disease
- Author
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2013
- Field of study
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma
Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease
- Author
- A Rodriguez
- A RodrĂguez
- A Rojek
- AM Rojek
- Amaia RodrĂguez
- B Blomme
- C Cai
- Catherine Brenner
- CC Li
- CS Lee
- DG Tiniakos
- DH Lee
- Donatella Mentino
- Elena Fanelli
- G Calamita
- G Calamita
- G Calamita
- G Calamita
- GE Liquori
- Gema FrĂŒhbeck
- Giuseppe Calamita
- H Kuriyama
- I Grattagliano
- J Badaut
- J Lebeck
- JM Carbrey
- KA Love-Osborne
- L Portois
- M Basaranoglu
- M Elkjaer
- M Hara-Chikuma
- M Krawczyk
- M Miranda
- Maria Mastrodonato
- Maria Svelto
- Michael MĂŒller
- N Chalasani
- N Maeda
- N Pastor-Soler
- P Agre
- P Gena
- Patrizia Gena
- Piero Portincasa
- RaĂșl A. Marinelli
- S Jelen
- S Jelen
- SQ Yang
- SQ Yang
- V Catalan
- W Dunn
- ZM Younossi
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- Field of study
Modulation of Aquaporins by Dietary Patterns and Plant Bioactive Compounds
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- Almasalmeh A.
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Increased water flux induced by an aquaporin-1/carbonic anhydrase II interaction
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- Anstee DJ
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- Benjamin Margolis
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- Publication venue
- 'American Society for Cell Biology (ASCB)'
- Publication date
- Field of study
New insights into the genetic etiology of Alzheimerâs disease and related dementias
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- Wright C. B.
- Wu C. -K.
- Wu Y.
- Xia T. -H.
- Xing Chen
- Xinli Hu
- Xiongwei Zhu
- Xu E.
- Xu F.
- Xuan Liu
- Yanbing Wang
- Yanek L.
- Yang Q.
- Yang Y.
- Yannakoulia M.
- Yaqub A.
- Yasaman Saba
- Yash Patel
- Yeunjoo E Song
- Yi Zhao
- Ying Wu
- Yoav Ben-Shlomo
- Yogen Patel
- Younkin S. G.
- Yu C. -E.
- Yu L.
- Yuanchao Zhang
- Yuk Yee Leung
- Yunfeng Huang
- Yunju Yang
- Zare H.
- Zdenka Pausova
- Zhang X.
- Zhang Y.
- Zhao Y.
- Zhao Y.
- Zhou W.
- Zhu C.
- Zhu X.
- Ziemann A.
- Zoia C. P.
- Zompo M. D.
- Zulaica M.
- Zulma Sevillano
- Ălvarez V.
- Ă sa Hedman
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimerâs disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/âproxyâ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A\u3b2, tau, immunity and lipid processing
- Author
- Abner Erin
- Adams Hieab H.
- Adams Perrie M.
- Ahmad Shahzad
- Al-Chalabi Ammar
- Albert Marilyn S.
- Albin Roger L.
- Allen Mariet
- Alvarez Ignacio
- Alvarez Victoria
- Amin Najaf
- Amlie-Wolf Alexandre
- Amouyel Phillippe
- Apostolova Liana G.
- Arnold Steven E.
- Aspelund Thor
- Asthana Sanjay
- Atwood Craig S.
- Avramidou Despoina
- Bacq Delphine
- Badarinarayan Nandini
- Baldwin Clinton T.
- Barber Robert C.
- Barnes Lisa L.
- Barral Sandra
- Bass Nicholas J.
- Bayer Anthony
- Beach Thomas G.
- Becker James T.
- Beecham Gary W.
- Beekly Duane
- Beiser Alexa S.
- Bellenguez Celine
- Ben-Shlomo Yoav
- Benito Yolanda A.
- Bennett David
- Berr Claudine
- Bigio Eileen H.
- Bird Thomas D.
- Bis Joshua C.
- Bisceglio Gina
- Blacker Deborah
- Boada Merce
- Boccardi Virginia
- Boerwinkle Eric
- Boeve Bradley F.
- Boland Anne
- Bonuccelli Ubaldo
- Bosco Paola
- Bossu Paola
- Bowen James D.
- Boxer Adam
- Bras Jose
- Brayne Carol
- Brice Alexis
- Brody Jennifer A.
- Brown Kristelle
- Brundin Rosemarie
- Bruni Amalia Cecilia
- Bullido Maria J.
- Burke James R.
- Burns Jeffrey M.
- Bush Will S.
- Butkiewicz Mariusz
- Buxbaum Joseph D.
- Caffarra Paolo
- Cairns Nigel J.
- Caltagirone Carlo
- Campion Dominique
- Cantwell Laura B.
- Cao Chuanhai
- Carlson Chris S.
- Carlsson Cynthia M.
- Carney Regina M.
- Carracedo Angel
- Carrasquillo Minerva M.
- Cecchetti Roberta
- Chen Yuning
- Choi Seung-Hoan
- Chouraki Vincent
- Chui Helena C.
- Ciaramella Antonio
- Clarimon Jordi
- Clarke Robert
- Collinge John
- Concari Letizia
- Corcoran Chris
- Coto Eliecer
- Craig David
- Crane Paul K.
- Cribbs David H.
- Crocco Elizabeth A.
- Cruchaga Carlos
- Cuccaro Michael L.
- Cupidi Chiara
- Cupples L. Adrienne
- Cushion Thomas D.
- Damotte Vincent
- Daniele Antonio
- Daniilidou Makrina
- Dartigues Jean-Francois
- De Deyn Peter Paul
- De Jager Phil L.
- de Rojas Itziar
- Debette Stphanie
- DeCarli Charles
- Del Zompo Maria
- Deleuze Jean-Francois
- Deloukas Panagiotis
- Denning Nicola
- Deramecourt Vincent
- DeStefano Anita L.
- Dichgans Martin
- Dick Malcolm
- Dickson Dennis W.
- Diez-Fairen Monica
- Dombroski Beth A.
- Doody Rachelle S.
- Drichel Dmitriy
- Duara Ranjan
- Dubois Bruno
- Dufouil Carole
- Eiriksdottir Gudny
- Engelborghs Sebastiaan
- Epelbaum Jacques
- Ertekin-Taner Nilifur
- Escott-Price Valentina
- Evans Denis A.
- Faber Kelley M.
- Fairchild Thomas J.
- Fallon Kenneth B.
- Fardo David W.
- Farlow Martin R.
- Farrer Lindsay A.
- Ferris Steven
- Feulner Thomas
- Fievet Nathalie
- Fin Bertrand
- Fisher Elizabeth
- Fitzpatrick Annette L.
- Fornage Myriam
- Foroud Tatiana M.
- Fox Nick C.
- Fratiglioni Laura
- Frisardi Vincenza
- Frizatti Aura
- Froelich Lutz
- Frosch Matthew P.
- Galasko Douglas R.
- Galimberti Daniela
- Gallacher John
- Gallo Maura
- Garcia Melissa E.
- Garnier Jean-Guillaume
- Garzia Fabienne
- Gearing Marla
- Germanou Antonia
- Gerrish Amy
- Geschwind Daniel H.
- Ghetti Bernardino
- Giedraitis Vilmantas
- Giegling Ina
- Gilbert John R.
- Gill Michael
- Gkatzima Olymbia
- Goate Alison M.
- Graff Caroline
- Graff-Radford Neill R.
- Green Robert C.
- Grenier-Boley Benjamin
- Growdon John H.
- Grozeva Detelina
- Gu Wei
- Gudnason Vilmundur
- Guerreiro Rita
- Gwilliam Rhian
- Haapasalo Annakaisa
- Haines Jonathan L.
- Hakonarson Hakon
- Hamilton Ronald L.
- Hamilton-Nelson Kara L.
- Hampel Harald
- Hannequin Didier
- Hanon Olivier
- Hardy John
- Harold Denise
- Harrell Lindy E.
- Hartmann Annette M.
- Helisalmi Seppo
- Hernandez Isabel
- Heun Reinhard
- Heuser Isabella
- Hiltunen Mikko
- Himali Jayanadra J.
- Hodges Angela
- Hofer Edith
- Hoffmann Per
- Hollingworth Paul
- Holmans Peter A.
- Holmes Clive
- Honig Lawrence S.
- Hooper Nigel M.
- Huebinger Ryan M.
- Huell Michael
- Huentelman Matthew J.
- Hughes Joseph T.
- Hulette Christine M.
- Hyman Bradley T.
- Ikram M. Arfan
- Ingelsson Martin
- Jakobsdottir Johanna
- Jarvik Gail P.
- Jessen Frank
- Jian Xueqiu
- Jin Lee-Way
- Joeckel Karl-Heinz
- Johnston Janet A.
- Jones Lesley
- Jun Gyungah R.
- Kamboh M. Ilyas
- Karamujic-Comic Hata
- Karydas Anna
- Katz Mindy J.
- Kauwe John S. K.
- Kawalia Amit
- Kaye Jeffrey A.
- Keene C. Dirk
- Kehoe Patrick G.
- Keller Lina
- Kilander Lena
- Kim Ronald
- Klopp Norman
- Kloszewska Iwona
- Koelsch Heike
- Koivisto Anne Maria
- Kornhuber Johannes
- Koutroumani Maria
- Kowall Neil W.
- Kramer Joel H.
- Kukull Walter A.
- Kunkle Brian W.
- Kuzma Amanda B.
- LaFerla Frank M.
- Lah James J.
- Lambert Jean-Charles
- Lannfelt Lars
- Larson Eric B.
- Launer Lenore J.
- Lawlor Brian
- Leber Markus
- Leonenko Ganna
- Leverenz James B.
- Levey Allan, I
- Li Shuo
- Lieberman Andrew P.
- Lin Honghuang
- Lipton Richard B.
- Livingston Gill
- Lleo Alberto
- Longstreth W. T., Jr.
- Lopez Oscar L.
- Lord Jenny
- Love Seth
- Lovestone Simon
- Lunetta Kathryn L.
- Lupton Michelle K.
- Lyketsos Constantine G.
- Lynch Aoibhinn
- Ma Li
- Maier Wolfgang
- Malamon John
- Maletta Raffaele Giovanni
- Mancuso Michelangelo
- Mann David
- Marshall Rachel
- Marson Daniel C.
- Martin Eden R.
- Martiniuk Frank
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- Masliah Eliezer
- Masullo Carlo
- Mateo Ignacio
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- McKee Ann C.
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- Mead Simon
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- Medway Christopher
- Meggy Alun
- Menzies Georgina E.
- Meslage Stphane
- Mesulam Marsel
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- Miller Carol A.
- Miller Joshua W.
- Moebus Susanne
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- Moreno-Grau Sonia
- Morgan Kevin
- Morgan Taniesha
- Morris John
- Morris John C.
- Mosley Thomas H.
- Moutet Marie-Laure
- Mukherjee Shubhabrata
- Munger Ron
- Munoz-Fernadez Carmen
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- Naj Adam C.
- Naranjo Maria Candida Deniz
- Nicolas Gael
- Noethen Markus M.
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- O'Donovan Michael C.
- Olaso Robert
- Olichney John M.
- Orellana Adelina
- Orfei Maria Donata
- Owen Michael J.
- Panza Francesco
- Parisi Joseph E.
- Pasquier Florence
- Passmore Peter
- Pastor Pau
- Patel Yogen
- Paulson Henry L.
- Pericak-Vance Margaret A.
- Perry William R.
- Peskind Elaine
- Peters Oliver
- Petersen Ronald C.
- Pickering-Brown Stuart
- Pierce Aimee
- Pilotto Alberto
- Poon Wayne W.
- Potter Huntington
- Powell John F.
- Proitsi Petra
- Psaty Bruce M.
- Qu Liming
- Quinn Joseph F.
- Quintela Ines
- Raj Ashok
- Ramirez Alfredo
- Raskind Murray
- Raybould Rachel
- Real Luis M.
- Reiman Eric M.
- Reisberg Barry
- Reisch Joan S.
- Reitz Christiane
- Riedel-Heller Steffi
- Riemenschneider Matthias
- Ringman John M.
- Ritchie Karen
- Rivadeneira Fernando
- Roberson Erik D.
- Rodriguez-Rodriguez Eloy
- Rogaeva Ekaterina
- Roschupkin Gena
- Rosen Howard J.
- Rosenberg Roger N.
- Rossor Martin
- Rotter Jerome, I
- Royall Donald R.
- Rubinsztein David C.
- Ruiz Agustin
- Russo Giancarlo
- Ryan Natalie S.
- Saba Yasaman
- Sacchinelli Eleonora
- Sager Mark A.
- Salani Francesca
- Sanchez-Garcia Florentino
- Sanchez-Juan Pascual
- Sano Mary
- Sarnowski Chloe
- Saykin Andrew J.
- Scarpini Elio
- Schellenberg Gerard D.
- Scherer Martin
- Schmidt Helena
- Schmidt Reinhold
- Schneider Julie A.
- Schneider Lori S.
- Schott Jonathan M.
- Seeley William W.
- Seshadri Sudha
- Shaw Christopher E.
- Sims Rebecca
- Singleton Andrew B.
- Sleegers Kristel
- Slifer Susan
- Smith A. David
- Smith Albert, V
- Smith Amanda G.
- Soininen Hilkka
- Solfrizzi Vincenzo
- Song Yuenjoo
- Sonnen Joshua A.
- Sorbi Sandro
- Sordon Sabrina
- Spalletta Gianfranco
- Spina Salvatore
- Squassina Alessio
- St George-Hyslop Peter
- Stern Robert A.
- Sussams Rebecca
- Swerdlow Russell H.
- Tang Mitchell
- Tanzi Rudolph E.
- Tarraga Lluis
- Thonberg Hakan
- Trojanowski John Q.
- Troncoso Juan C.
- Tschanz JoAnn
- Tsolaki Magda
- Tsuang Debby W.
- Turton James
- Uitterlinden A. G. Andre
- Uphill James
- Valladares Otto
- Van Broeckhoven Christine
- Van Deerlin Vivianna M.
- van den Bussche Hendrik
- van der Lee Sven J.
- van Duijn Cornelia M.
- Van Eldik Linda J.
- Vance Jeffery M.
- Vandenberghe Rik
- Vardarajan Badri N.
- Vardy Emma
- Vellas Bruno
- Vinters Harry V.
- Voijnovic Dina
- Vonsattel Jean Paul
- Vronskaya Maria
- Wallon David
- Wang Li-San
- Warden Donald
- Warner Nick
- Warren Jason D.
- Weintraub Sandra
- Welsh-Bohmer Kathleen A.
- White Charles C.
- Whitehead Patrice
- Wichmann H-Erich
- Wilcock Gordon
- Wilhelmsen Kirk C.
- Williams Julie
- Williamson Jennifer
- Wiltfang Jens
- Wingo Thomas S.
- Woltjer Randall L.
- Wright Clinton B.
- Wu Chuang-Kuo
- Yang Qiong
- Younkin Steven G.
- Yu Chang-En
- Yu Lei
- Zhao Yi
- Publication venue
- Publication date
- 01/01/2019
- Field of study
New insights into the genetic etiology of Alzheimerâs disease and related dementias
- Author
- Aaltonen Lauri
- Aaltonen Vesa
- Aarsland Dag
- Aavikko Mervi
- Abalos Mariana Sanchez
- Abdelnour Carla
- Abner Erin
- Abraham Richard
- Adams Hieab
- Adams Perrie M.
- Adarmes-GĂłmez Ad
- Adarmes-GĂłmez Astrid D.
- Aguilera Nuria
- Aguilera Nuria
- Aguirre Alyssa
- Ahmad Shahzad
- Akinyemi Rufus O.
- Al-Chalabi Ammar
- AlarcĂłn-MartĂn Emilio
- Albert Marilyn S.
- Albin Roger L.
- Alcolea Daniel
- Alegret Montserrat
- Ali Muhammad
- Allen Mariet
- Allende Irene Rosas
- Alonso MarĂa Dolores
- Alonso MarĂa Dolores
- Alvarez Ignacio
- Alvarez Lisa
- Amer-Ferrer Guillermo
- Amin Najaf
- Amouyel Philippe
- Anastasiou Anna
- Anastasiou Costas
- Andrade Victor
- Andreassen Ole A.
- Andreoni Simona
- Antequera Martirio
- Antikainen Riitta
- Antonell Anna
- Anttonen Vuokko
- AntĂșnez Carmen
- Aparicio Hugo J.
- Apostolova Liana G.
- Appollonio Ildebrando
- Arcaro Marina
- Archetti Silvana
- Armstrong Nicola
- Armstrong Nicola J.
- Arnold Steven E.
- Arosio Beatrice
- Arvas Mikko
- Assogna Francesca
- Asthana Sanjay
- Athanasiu Lavinia
- Atwood Craig S.
- Auge Franck
- Auranen Annika
- Auvinen PĂ€ivi
- Awaisa Ghazal
- Ayres Gayle
- Bacha Juan Ignacio
- Bahadori Maryam
- Bahrami Shahram
- Bailly Henri
- Baldwin Clinton T.
- Banaj Nerisa
- Baquero Miquel
- Barber Robert C.
- Barnes Lisa L.
- Barral Sandra
- Barral Sandra
- Bass Nicholas J.
- Bass Nick
- Bastiani Patrizia
- Bayer Anthony
- Beach Thomas G.
- Becker James T.
- Becker James T.
- Becker Tim
- Beecham Gary W.
- Beekly Duane
- Behrens Tim
- Beiser Alexa
- Belezhanska Diyana
- Bellenguez CĂ©line
- Below Jennifer E.
- Below Jennifer E.
- Ben-Shlomo Yoav
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- Sotolongo-Grau Oscar
- Spallazzi Marco
- Spalletta Gianfranco
- Spina Salvatore
- Spottke Annika
- Squassina Alessio
- Stern Robert A.
- Stevens Alan B.
- Stordal Eystein
- Strandberg Timo
- Strauss Erich
- Strittmatter Stephen M.
- StÄhlbom Anne Kinhult
- Sultzer David
- Suominen Liisa
- Sussams Rebecca
- Swerdlow Russell H.
- SĂĄez MarĂa Eugenia
- SĂĄnchez-Arjona MarĂa Bernal
- SĂĄnchez-Valle Raquel
- Takalo Mari
- Tanzi Rudolph E.
- Tartan Juan Pablo
- Tasanen Kaisa
- Taskinen Marja-Riitta
- Teipel Stefan
- Teng Edmond
- TesĂ Niccolo
- Teumer Alexander
- Thalamuthu Anbupalam
- Thomas Alvin
- Thomas Charlene
- Thomas Tegos
- Thomassen Jesper Qvist
- Thonberg HĂ„kan
- Tienari Pentti
- Tilson Jeffrey L.
- Tin Adrienne
- Todd Stephen
- Toso Carlos Reyes
- Tosto Giuseppe
- Traykov Latchezar
- Tremolizzo Lucio
- Trojanowski John Q.
- Troncoso Juan C.
- Tsai Ellen
- Tsolaki Anthoula
- Tsolaki Magda
- Tsuang Debby W.
- Tsuo Kristin
- Tucker-Drob Elliot
- Tukiainen Taru
- Tuomi Tiinamaija
- Tuomilehto Jaakko
- Tuovila Outi
- Turpeinen Miia
- Turton James
- Turunen Joni A.
- TybjĂŠrg-Hansen Anne
- Tzourio Christophe
- TĂĄrraga LluĂs
- Uitterlinden Andre
- Ullgren Abbe
- Ulstein Ingun
- Uphill James
- Usiskin Keith
- Uusitalo Hannu
- Uusitalo-JĂ€rvinen Hannele
- Vacca Alessandro
- Vainio Seppo
- Valero Sergi
- Valladares Otto
- Valladares Otto
- van Adelsberg Janet
- Van Deerlin Vivianna M.
- van den Bussche Hendrik
- van der Flier Wiesje M.
- van der Lee Sven J.
- van der Lugt Aad
- van Duijn Cornelia M.
- van Eldik Linda J.
- van Lent Debora Melo
- van Rooij Jeroen
- van Swieten John
- Vance Jeffery
- Vandenberghe Rik
- Vardarajan Badri N.
- Vardy Emma
- Vargas Liliana
- Vassar Robert
- Verhey Frans
- Vicente Maria Pilar
- Vidal Jean-SĂ©bastien
- Vigo-Ortega R.
- Vigo-Ortega Rosario
- Vilas Raquel Huerto
- Vinters Harry V.
- Virolainen Petri
- Vivancos Liliana
- Vogelgsang Jonathan
- Vojinovic Dina
- Vonsattel Jean-Paul
- Voutilainen Markku
- Vyhnalek Martin
- Wadhawan Samir
- Wagner Michael
- Wallon David
- Wang Clarence
- Wang Li-San
- Wang Ruiqi
- Wang Yanbing
- Warden Donald
- Waring Jeff
- Waring Jeffrey
- Warner Nick
- Warren Jason D.
- Waterworth Dawn
- Weber Heike
- Weinhold Leonie
- Weinstein Galit
- Weintraub Sandra
- Welsh-Bohmer Kathleen A.
- Whelan Christopher
- Whitehead Patrice L.
- Wichmann H-Erich
- Wigmore Eleonor
- Wijsman Ellen M.
- Wilcock Gordon
- Wilhelmsen Kirk C.
- Williams Amy
- Williams Benjamin
- Williams Dylan
- Williams Julie
- Williamson Jennifer
- Wilms Henrik
- Wiltfang Jens
- Windle Gill
- Wingo Thomas S.
- Wisniewski Thomas
- Wittfeld Katharina
- Woltjer Randall L.
- Wong Regis
- Woods Bob
- Woon Martin
- Wright Clinton B.
- Wu Chuang-Kuo
- Wu Ying
- Xia Tai-he
- Xu Ethan
- Xu Fanli
- Yanek Lisa
- Yang Qiong
- Yang Yunju
- Yannakoulia Mary
- Yaqub Amber
- Younkin Steven G.
- Yu Chang-En
- Yu Lei
- Zare Habil
- Zhang Xiaoling
- Zhang Yuanchao
- Zhao Yi
- Zhao Yi
- Zhou Wei
- Zhu Congcong
- Zhu Xiongwei
- Ziemann Adam
- Zoia Chiara Paola
- Zompo Maria Del
- Zulaica Miren
- Ălvarez Victoria
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/04/2022
- Field of study
Characterization of the genetic landscape of Alzheimerâs disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/âproxyâ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele