8 research outputs found
New insights into the genetic etiology of Alzheimer's disease and related dementias
- Author
- Aaltonen L.
- Aaltonen V.
- Aarsland Dag
- Aavikko M.
- Abalos M.S.
- Abdelnour Carla
- Abner E.
- Abraham R.
- Adams H.
- Adams P.M.
- Adarmes-GĂłmez A.
- Adarmes-GĂłmez A.D.
- Aguilera N.
- Aguilera N.
- Aguirre A.
- Ahmad S.
- Akinyemi R.O.
- Al-Chalabi A.
- AlarcĂłn-MartĂn Emilio
- Albert M.S.
- Albin R.L.
- Alcolea Daniel
- Alegret Montserrat
- Ali M.
- Allen M.
- Allende I.R.
- Alonso M.D.
- Alonso M.D.
- Alvarez I.
- Alvarez L.
- Amer-Ferrer G.
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- Amouyel Philippe
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- Universitat AutĂČnoma de Barcelona
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- Zulaica M.
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- Publication venue
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer's 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/'proxy' 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
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
- Author
- Aarsland Dag
- Aarsland Dag
- Abdelnour Carla
- Abraham Richard
- Abraham Richard
- Adarmes-GĂłmez A.D.
- Adarmes-GĂłmez Ad
- Aguilera N.
- Aguilera Nuria
- Ahmad Shahzad
- Al-Chalabi Ammar
- Al-Chalabi Ammar
- Alarcon E.
- AlarcĂłn-MartĂn E.
- AlarcĂłn-MartĂn Emilio
- Alcolea Daniel
- Alegret M.
- Alegret Montserrat
- Alonso M.D.
- Alvarez Ignacio
- Alvarez Victoria
- Ambati Aditya
- Amer-Ferrer G.
- Amin Najaf
- Amouyel Philippe
- Amouyel Philippe
- Amouyel Phillippe
- Anastasiou Anna
- Anastasiou Costas
- Andrade Victor
- Andreassen Ole A.
- Andreassen Ole A.
- Andreassen Ole A.
- Andreoni Simona
- Annuar Azlina Ahmad
- Antequera M.
- Anthoula Tsolaki
- Antikainen Riitta
- Antonell Anna
- AntĂșnez C.
- Appollonio Ildebrando
- Arcaro Marina
- Archetti Silvana
- Arfan Ikram M.
- Arias Pastor Alfonso
- Ariel Prestia Federico
- Armstrong Nicola J.
- Arosio Beatrice
- Arosio Beatrice
- Assogna Francesca
- Athanasiu Lavinia
- Athanasiu Lavinia
- Au Wing-Lok
- Bahrami Shahram
- Bailly Henri
- Banaj Nerisa
- Baquero M.
- Baquero Miquel
- Bass Nicholas J.
- Bass Nick
- Bastiani Patrizia
- Bayer Anthony
- Becker Tim
- Belezhanska Diyana
- Bellenguez CĂ©line
- Bellenguez CĂ©line
- Bellenguez CĂ©line
- Belloy Michael E.
- Belén Pastor Ana
- Ben-Shlomo Yoav
- Benussi Alberto
- Benussi Luisa
- Benussi Luisa
- Bergh Sverre
- Bernal M.
- Bernardo-Harrington Mateus
- Berr Claudine
- Berr Claudine
- Besse CĂ©line
- Bessi Valentina
- Binetti Giuliano
- Bizarro Alessandra
- Bjerke Maria
- Blennow Kaj
- Blesa R.
- Blesa Rafael
- Boada M.
- Boada M.
- Boada MercĂš
- Boada MercĂš
- Boecker Henning
- Boland Anne
- Boland Anne
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- Borroni Barbara
- Boschi Silvia
- Bosnes Ingunn
- BossĂč Paola
- Brayne Carol
- Brayne Carol
- Bresner Catherine
- Brice Alexis
- Brodaty Henry
- Brookes Keeley J.
- Brown Kristelle
- Brown Kristelle S.
- BrÄthen Geir
- BrÄthen Geir
- Buendia M.
- Buendia Mar
- Buiza-Rueda D.
- Buiza-Rueda Dolores
- Bullido M.J.
- Bullido MarĂa J.
- Bullido MarĂa J.
- Burguera J.A.
- Burholt Vanessa
- BĂrger Katharina
- Caffarra Paolo
- Calero M.
- Calero Miguel
- campion Dominique
- Campos-Martin Rafael
- Cano A.
- Carracedo A.
- Carracedo Ăngel
- Carrillo F.
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- CarriĂłn-Claro M.
- Casajeros M.J.
- Castaño Eduardo M.
- Castillo Morales Atahualpa
- Cañabate P.
- Cañabate Pilar
- Cecchetti Roberta
- Cervera-Carles Laura
- Chan Anne Y.Y.
- Chao Yinxia
- Chapuis Julien
- Charbonnier Camille
- Chen Ling
- Chen Yongping
- Chene GeneviĂšve
- Chew Elaine Guo Yan
- Chillotti Caterina
- Chipi Elena
- Chung Sun Ju
- Ciccone Simona
- Ciullo Valentina
- Claassen Jurgen A.H.R.
- Clarimon Jordi
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- Clark Christopher
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- Conti Elisa
- CorbatĂłn-Anchuelo A.
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- Costa Marcos R
- Costantini Emanuele
- Craig David
- Craig David
- Cruz-Gamero J.M.
- Cuesta Carolina
- Custodero Carlo
- Daian Delphine
- Dalmasso Maria Carolina
- Damotte Vincent
- Damotte Vincent
- Daniele Antonio
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- Dardiotis Efthimios
- Darling Daniel
- Dartigues Jean-Francois
- Dartigues Jean-François
- David Smith A.
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- de Munain Adolfo Lopez
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- de Rojas Itziar
- de Rojas Itziar
- Debette Stéphanie
- Debette Stéphanie
- Deckert JĂŒrgen
- del Ser T.
- del Ser Teodoro
- Del Zompo Maria
- Deleuze Jean-François
- Deleuze Jean-François
- Deloukas Panagiotis
- Deloukas Pangiotis
- den Bussche Hendrik
- Denning Nicola
- Denning Nicola
- Deramecourt Vincent
- Dermecourt Vincent
- Dichgans Martin
- Dichgans Martin
- Dichgans Martin
- Diego S.
- Diego Susana
- Diehl-Schmid Janine
- Diez-Fairen M.
- Diez-Fairen MĂłnica
- Dionigi Rossi Paolo
- Djurovic Srdjan
- Djurovic Srdjan
- Dolores Alonso MarĂa
- Dowzell Kimberley
- Drichel Dmitriy
- Dubois Bruno
- Dufouil Carole
- Dufouil Carole
- Dufouil Carole
- During Emmanuel
- Duron Emmanuelle
- DĂŒzel Emrah
- DĂŒzel Emrah
- Engelborghs Sebastiaan
- Epelbaum Jacques
- Escott-Price Valentina
- Escott-Price Valentina
- Escuela R.
- Escuela R.
- Espinosa A.
- Espinosa Ana
- Etchepareborda Ignacio
- Eugenia SĂĄez MarĂa
- Ewers Michael
- Fabrizio Tagliavini
- Fallgaard Nielsen Sune
- Farotti Lucia
- Fenoglio Chiara
- FernĂĄndez-Fuertes Marta
- Ferrarese Carlo
- Ferreira Catarina B
- Ferri Evelyn
- Feulner Thomas
- Fievet Nathalie
- Fievet Nathalie
- Fin Bertrand
- Fischer Peter
- Fisher Elizabeth
- Fladby Tormod
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- Foo Jia Nee
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- Forsell Charlotte
- Fortea J.
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- Fox Nick
- Fox Nick C.
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- Franco E.
- Franco-MacĂas Emlio
- Frank-GarcĂa A.
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- Frikke-Schmidt Ruth
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- Froelich Lutz
- Frölich Lutz
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- Galeano Pablo
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- Gan-Or Ziv
- Garcia Madrona S.
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- Garcia-Ribas Guillermo
- Garcia-Ribas Guillermo
- GarcĂa-Alberca J.M.
- GarcĂa-Alberca JosĂ© MarĂa
- GarcĂa-GonzĂĄlez P.
- GarcĂa-GonzĂĄlez Pablo
- GarcĂa-GonzĂĄlez Pablo
- Garrote-Espina L.
- Garrote-Espina L.
- Germani Sandra
- Gerrish Amy
- Gerrish Amy
- Ghanbari Mohsen
- Ghidoni Roberta
- Giedraitis Vilmantas
- Giedraitis Vilmantas
- Giegling Ina
- Giegling Ina
- Gill Michael
- Gill Michael
- Gill Michael
- Gim Jungsoo
- Giorgio Giaccone
- Goldhardt Oliver
- Goldhardt Oliver
- GonzĂĄlez-PĂ©erez A.
- GonzĂĄlez-PĂ©rez Antonio
- Graff Caroline
- Graff Caroline
- Grande Giulia
- Green Emma
- Greicius Michael D.
- Grenier-Boley Benjamin
- Grenier-Boley Benjamin
- Grenier-Boley Benjamin
- Grimmer Timo
- GrĂŒnblatt Edna
- GrĂŒnblatt Edna
- Gu Wei
- Guerreiro Rita
- Guetta-Baranes Tamar
- Guitart M.
- Guitart Marina
- Gurling Hugh
- Gwilliam Rhian
- Gwilliam Rhian
- GĂłmez-Garre P.
- GĂłmez-Garre P.
- Haapasalo Annakaisa
- Hadjigeorgiou Georgios
- Hampel Harald
- Hampel Harald
- Hannequin Didier
- Hanon Olivier
- Hanon Olivier
- Hanon Olivier
- Hardy John
- Hardy John
- Hardy John
- Harold Denise
- Harold Denise
- Hartmann Annette M.
- Hartmann Annette M.
- Harwood Janet
- Hausner Lucrezia
- Hausner Lucrezia
- He Zihuai
- Heilmann-Heimbach Stefanie
- Heilmann-Heimbach Stefanie
- Helisalmi Seppo
- Heneka Michael T.
- HernĂĄndez Isabel
- Herold Christine
- Herrmann Martin J.
- Heun Reinhard
- Heuser Isabella
- Hevilla S.
- Hiltunen Mikko
- Hiltunen Mikko
- Hodges Angela
- Hoffmann Per
- Hoffmann Per
- Hollingworth Paul
- Hollingworth Paul
- Holmans Peter
- Holmans Peter A.
- Holmes Clive
- Holmes Clive
- Holstege Henne
- Holstege Henne
- Hooper Nigel M.
- Hort Jakub
- Hort Jakub
- Huerto Vilas Raquel
- Hulsman Marc
- HĂŒll Michael
- Ibarria M.
- Ibarria Marta
- Ignacio Bacha Juan
- Ignacio Brusco Luis
- Ikeuchi Takeshi
- Ingelsson Martin
- Ingelsson Martin
- Ingino Carlos
- Jan Biessels Geert
- Janowitz Daniel
- Jansen Iris
- Jansen Iris
- Jeon Beom S.
- Jessen Frank
- Jessen Frank
- Jessen Frank
- JesĂșs S.
- JesĂșs S.
- Jiang Lulu
- Johansson Charlotte
- Johnston Janet A.
- Johnston Jarret A.
- Jones Lesley
- Jones Lesley
- Jung Yoo Jin
- Jöckel Karl-Heinz
- JĂŒrgen Deckert
- Kauwe John
- Kehoe Patrick
- Kehoe Patrick G.
- Kehoe Patrick G.
- Kern Silke
- Khor Chiea Chuen
- Kilander Lena
- Kinhult StÄhlbom Anne
- Kivipelto Miia
- Kleineidam Luca
- Klopp Norman
- Kochen Silvia
- Koh Woon-Puay
- Kohler Eduardo
- Kohler Matias
- Koivisto Anne
- Kornhuber Johannes
- Kornhuber Johannes
- Kosmidis Mary H.
- Kuulasmaa Teemu
- Kuulasmaa Teemu
- Kölsch Heike
- KĂŒĂ§ĂŒkali Fahri
- KĂŒĂ§ĂŒkali Fahri
- Laatikainen Tiina
- Labrador Espinosa M.A.
- Labrador Ma
- Lacidogna Giordano
- Lacour ndré
- Laczo Jan
- Lafuente A.
- Lafuente AsunciĂłn
- Lage C.
- Lage Carmen
- Lage Carmen
- Lambert Jean-Charles
- Lambert Jean-Charles
- Lambert Jean-Charles
- Laske Christoph
- Laukka Erika J
- Lauria Alessandra
- Lawlor Brian
- Lawlor Brian
- Le Guen Yann
- Lee Kun Ho
- Legaz A.
- Lehtisalo Jenni
- Lerch Ondrej
- Lian Michelle M.
- Lian Michelle Mulan
- Lim Jia Lun
- Lim Shen-Yang
- Lin Juei-Jueng
- Lin Ling
- Lindström Jaana
- Lis Palacio Dana
- Lisso Julieta
- Liu Chunfeng
- Liu Jianjun
- Livingston Gill
- Livingston Gill
- LleĂł Alberto
- LleĂło A.
- Lord Jenny
- Love Seth
- Love Seth
- Lovestone Simon
- Lovestone Simon
- Luckcuck Lauren
- Luckcuck Lauren
- Luis Royo Jose
- Luo Guo
- Lupton Michelle
- Lupton Michelle
- LuĂs Royo Jose
- Lynch Aoibhinn
- Lynch Aoibhinn
- LĂłopez de MunĂĄin A.
- LĂłpez-GarcĂa S.
- LĂłpez-GarcĂa Sara
- Löwemark Malin
- Macias J.
- Macias-GarcĂa D.
- Macias-GarcĂa D.
- MacLeod Catherine A.
- MacĂas Juan
- Magda Tsolaki
- Maier Wolfgang
- Maier Wolfgang
- Malik Rainer
- Mangialasche Francesca
- Mangone Carlos
- Mann David
- Mann David
- Manzanares S.
- Mao Chengjie
- Marco Spallazzi
- Maria GarcĂa-Alberca Jose
- Maroñas O.
- Marquié M.
- Marquié M.
- Marquié Marta
- Marshall Rachel
- Marshall Rachel
- MartĂn Montes A.
- MartĂn Montes Angel
- MartĂn E.
- MartĂn Elvira
- MartĂnez RodrĂguez Carmen
- MartĂnez B.
- MartĂnez C.
- MartĂnez M.T.
- MartĂnez V.
- MartĂnez-Lage Ălvarez A.
- MarĂn M.
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- MarĂn T.
- MarĂn-Muñoz J.
- Masullo Carlo
- Masullo Carlo
- Mata Ignacio
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- Matoska Vaclav
- MauleĂłn Ana
- Mayhaus Manuel
- Mayo Kevin
- McGuinness Bernadette
- McGuinness Bernadette
- McQuillin Andrew
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- Mead Simon
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- Meah Wee-Yang
- Mecocci Patrizia
- Mecocci Patrizia
- Medel Nancy
- Medina M.
- Medina Miguel
- Meggy Alun
- Meggy Alun
- Mehrabian Shima
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- Mendioroz Iriarte M.
- Mendoza Silvia
- Menéndez-Gonzålez M.
- Menéndez-Gonzålez Manuel
- Mignot Emmanuel
- Mir P.
- Mir Pablo
- Mir Pablo
- Miyashita Akinori
- Moebus Susanne
- Moebus Susanne
- Moebus Susanne
- Mok Shi Qi
- Mok Vincent
- Mol Merel
- Molina-Porcel Laura
- Montrreal L.
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- Moreno Fermin
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- Morris John
- Muchnik Carolina
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- Möthen Markus M
- Nacmias Benedetta
- Nacmias Benedetta
- Naito Tatsuhiko
- Nash William
- Natunen Teemu
- Ng Ebonne Y.
- Ngandu Tiia
- Nicolas Aude
- Nicolas Gael
- Nicolas Gael
- Niida Shumpei
- Nordestgaard BĂžrge G.
- Nordestgaard BĂžrge G.
- Novack Gisela
- Nuñez-Llaves R.
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- O'Donovan Michael
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- Olaso Robert
- Olivar Natividad
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- Ortega G.
- Ortega Gemma
- Ortiz Cecilia
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- Ozaki Kouichi
- Pablo Tartan Juan
- Padovani Alessandro
- Pancho A.
- Pancho Ana
- Paola Zoia Chiara
- Paolo Caffarra
- Papenberg Goran
- Papenberg Goran
- Papma Janne
- Park Hyeonseul
- Parnetti Lucilla
- Parnetti Lucilla
- Parveen Kayenat
- Parveen Kayenat
- Pasquier Florence
- Pasquier Florence
- Pasquier Florence
- Passmore Peter
- Passmore Peter
- Pastor P.
- Pastor Pau
- Pastor Pau
- Patel Yogen
- Pei Zhong
- Peixoto Leal Thiago
- PelejĂ E.
- PelejĂ Esther
- Peltonen Markku
- Peng Rong
- Pericard Pierre
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- Pijnenburg Yolande A. L.
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- Pinchler Sabrina
- Pineda J.A.
- Pineda Juan A.
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- Thalamuthu Anbupalam
- Thomas Charlene
- Thomas Tegos
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- Toda Tatsushi
- Todd Stephen
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- Tsolaki Magda
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- TybjĂŠrg-Hansen Anne
- Tzourio Christophe
- TĂĄarraga L.
- TĂĄrraga LluĂs
- Uitterlinden Andre
- Ullgren Abbe
- Ulstein Ingun
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- Uphill James
- Vacca Alessandro
- Valero S.
- Valero S.
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- van der Flier Wiesje
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- Vicente M.P.
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- Vigo-Ortega R.
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- Vivancos L.
- Vogelgsang Jonathan
- Vyhnalek Martin
- Vyhnalek Martin
- Waern Margda
- Wagner Michael
- Wallon David
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- Warren Jason D.
- Weber Heike
- Weinhold Leonie
- Wichmann H-Erich
- Wilcock Gordon
- Williams Amy
- Williams Julie
- Williams Julie
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- Wiltfang Jens
- Wiltfang Jens
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- Windle Gill
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- Yan Yaping
- Yang Jing
- Yannakoulia Mary
- Yaqub Amber
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- Yu Eric
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- Zettergren Anna
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- Zulaica Miren
- Ălvarez I.
- Ălvarez V.
- Ălvarez Victoria
- Publication venue
- National Academy of Sciences
- Publication date
- 29/08/2023
- Field of study
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs 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 AÎČ42. 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
Desarrollo adaptativo y funcionamiento ejecutivo en niños con diagnóstico de trastorno disocial y trastorno de déficit de atención/hiperactividad tipo hiperactivo-impulsivo
- Publication venue
- Asoc. Espanola de Psicologia Clinica y Psicopatologia
- Publication date
- 01/01/2019
- Field of study
El desarrollo adaptativo permite al sujeto el control emocional, la disposiciĂłn hacia nuevos retos y el ajuste socio-cognitivo esperado contextualmente, facilitando el aprendizaje, funcionamiento ejecutivo y social. El objetivo del estudio fue [email protected]
Desarrollo adaptativo y funcionamiento ejecutivo en niños con diagnóstico de trastorno disocial y trastorno de déficit de atención/hiperactividad tipo hiperactivo-impulsivo
- Publication venue
- Asoc. Espanola de Psicologia Clinica y Psicopatologia
- Publication date
- 01/01/2019
- Field of study
El desarrollo adaptativo permite al sujeto el control emocional, la disposiciĂłn hacia nuevos retos y el ajuste socio-cognitivo esperado contextualmente, facilitando el aprendizaje, funcionamiento ejecutivo y social. El objetivo del estudio fue [email protected]
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
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- Aarsland D.
- Abdelnour C.
- Abdelnour C.
- Adarmes-GĂłmez A. D.
- Aguilera N.
- Alarcon E.
- AlarcĂłn-MartĂn E.
- AlarcĂłn-MartĂn E.
- Alcolea D.
- Alegret M.
- Alegret M.
- Alonso M. D.
- Alvarez I.
- Amer-Ferrer G.
- Amouyel P.
- Anastasiou A.
- Anastasiou C.
- Andrade V.
- Andreassen O.A.
- Andreoni S.
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- Antikainen R.
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- Publication venue
- 'Nature Research Society'
- Publication date
- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery nâ=â409,435 and validation size nâ=â58,190). Here, we add six variants associated with Alzheimerâs disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimerâs disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimerâs disease
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimerâs disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimerâs disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimerâs disease. © 2021, The Author(s)
Common variants in Alzheimerâs disease and risk stratification by polygenic risk scores
- Publication venue
- Publication date
- 01/01/2021
- Field of study
Genetic discoveries of Alzheimerâs disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimerâs disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimerâs disease patients in APOE É4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimerâs disease. © 2021, The Author(s)
New insights into the genetic etiology of Alzheimerâs disease and related dementias
- 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. © 2022, The Author(s)