KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease-Reference-Cited by-同舟云学术

KL-VS heterozygosity is associated with lower amyloid-dependent tau accumulation and memory impairment in Alzheimer’s disease

Published:2021-06-22 Issue:1 Volume:12 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Neitzel Julia^ORCID,Franzmeier Nicolai^ORCID,Rubinski Anna,Dichgans Martin^ORCID,Brendel Matthias^ORCID,Weiner Michael,Aisen Paul,Petersen Ronald,Jack Clifford R.,Jagust William,Trojanowki John Q.,Toga Arthur W.,Beckett Laurel,Green Robert C.,Saykin Andrew J.,Morris John,Shaw Leslie M.,Liu Enchi,Montine Tom,Thomas Ronald G.,Donohue Michael,Walter Sarah,Gessert Devon,Sather Tamie,Jiminez Gus,Harvey Danielle,Bernstein Matthew,Fox Nick,Thompson Paul,Schuff Norbert,DeCArli Charles,Borowski Bret,Gunter Jeff,Senjem Matt,Vemuri Prashanthi,Jones David,Kantarci Kejal,Ward Chad,Koeppe Robert A.,Foster Norm,Reiman Eric M.,Chen Kewei,Mathis Chet,Landau Susan,Cairns Nigel J.,Householder Erin,Reinwald Lisa Taylor,Lee Virginia,Korecka Magdalena,Figurski Michal,Crawford Karen,Neu Scott,Foroud Tatiana M.,Potkin Steven,Shen Li,Kelley Faber,Kim Sungeun,Nho Kwangsik,Kachaturian Zaven,Frank Richard,Snyder Peter J.,Molchan Susan,Kaye Jeffrey,Quinn Joseph,Lind Betty,Carter Raina,Dolen Sara,Schneider Lon S.,Pawluczyk Sonia,Beccera Mauricio,Teodoro Liberty,Spann Bryan M.,Brewer James,Vanderswag Helen,Fleisher Adam,Heidebrink Judith L.,Lord Joanne L.,Mason Sara S.,Albers Colleen S.,Knopman David,Johnson Kris,Doody Rachelle S.,Meyer Javier Villanueva,Chowdhury Munir,Rountree Susan,Dang Mimi,Stern Yaakov,Honig Lawrence S.,Bell Karen L.,Ances Beau,Morris John C.,Carroll Maria,Leon Sue,Mintun Mark A.,Schneider Stacy,OliverNG Angela,Griffith Randall,Clark David,Geldmacher David,Brockington John,Roberson Erik,Grossman Hillel,Mitsis Effie,deToledo-Morrell Leyla,Shah Raj C.,Duara Ranjan,Varon Daniel,Greig Maria T.,Roberts Peggy,Albert Marilyn,Onyike Chiadi,D’Agostino Daniel,Kielb Stephanie,Galvin James E.,Pogorelec Dana M.,Cerbone Brittany,Michel Christina A.,Rusinek Henry,de Leon Mony J.,Glodzik Lidia,De Santi Susan,Doraiswamy P. Murali,Petrella Jeffrey R.,Wong Terence Z.,Arnold Steven E.,Karlawish Jason H.,Wolk David,Smith Charles D.,Jicha Greg,Hardy Peter,Sinha Partha,Oates Elizabeth,Conrad Gary,Lopez Oscar L.,Oakley MaryAnn,Simpson Donna M.,Porsteinsson Anton P.,Goldstein Bonnie S.,Martin Kim,Makino Kelly M.,Ismail M. Saleem,Brand Connie,Mulnard Ruth A.,Thai Gaby,Mc Adams Ortiz Catherine,Womack Kyle,Mathews Dana,Quiceno Mary,Arrastia Ramon Diaz,King Richard,Weiner Myron,Cook Kristen Martin,DeVous Michael,Levey Allan I.,Lah James J.,Cellar Janet S.,Burns Jeffrey M.,Anderson Heather S.,Swerdlow Russell H.,Apostolova Liana,Tingus Kathleen,Woo Ellen,Silverman Daniel H. S.,Lu Po H.,Bartzokis George,Radford Neill R. Graff,ParfittH Francine,Kendall Tracy,Johnson Heather,Farlow Martin R.,Hake Ann Marie,Matthews Brandy R.,Herring Scott,Hunt Cynthia,van Dyck Christopher H.,Carson Richard E.,MacAvoy Martha G.,Chertkow Howard,Bergman Howard,Hosein Chris,Black Sandra,Stefanovic Bojana,Caldwell Curtis,Hsiung Ging Yuek Robin,Feldman Howard,Mudge Benita,Past Michele Assaly,Kertesz Andrew,Rogers John,Trost Dick,Bernick Charles,Munic Donna,Kerwin Diana,Mesulam Marek Marsel,Lipowski Kristine,Wu Chuang Kuo,Johnson Nancy,Sadowsky Carl,Martinez Walter,Villena Teresa,Turner Raymond Scott,Johnson Kathleen,Reynolds Brigid,Sperling Reisa A.,Johnson Keith A.,Marshall Gad,Frey Meghan,Yesavage Jerome,Taylor Joy L.,Lane Barton,Rosen Allyson,Tinklenberg Jared,Sabbagh Marwan N.,Belden Christine M.,Jacobson Sandra A.,Sirrel Sherye A.,Kowall Neil,Killiany Ronald,Budson Andrew E.,Norbash Alexander,Johnson Patricia Lynn,Obisesan Thomas O.,Wolday Saba,Allard Joanne,Lerner Alan,Ogrocki Paula,Hudson Leon,Fletcher Evan,Carmichael Owen,Olichney John,DeCarli Charles,Kittur Smita,Borrie Michael,Lee T. Y.,Bartha Rob,Johnson Sterling,Asthana Sanjay,Carlsson Cynthia M.,Potkin Steven G.,Preda Adrian,Nguyen Dana,Tariot Pierre,Reeder Stephanie,Bates Vernice,Capote Horacio,Rainka Michelle,Scharre Douglas W.,Kataki Maria,Adeli Anahita,Zimmerman Earl A.,Celmins Dzintra,Brown Alice D.,Pearlson Godfrey D.,Blank Karen,Anderson Karen,Santulli Robert B.,Kitzmiller Tamar J.,Schwartz Eben S.,SinkS Kaycee M.,Williamson Jeff D.,Garg Pradeep,Watkins Franklin,Ott Brian R.,Querfurth Henry,Tremont Geoffrey,Salloway Stephen,Malloy Paul,Correia Stephen,Rosen Howard J.,Miller Bruce L.,Mintzer Jacobo,Spicer Kenneth,Bachman David,Finger Elizabether,Pasternak Stephen,Rachinsky Irina,Drost Dick,Pomara Nunzio,Hernando Raymundo,Sarrael Antero,Schultz Susan K.,Ponto Laura L. Boles,Shim Hyungsub,Smith Karen Elizabeth,Relkin Norman,Chaing Gloria,Raudin Lisa,Smith Amanda,Fargher Kristin,Raj Balebail Ashok,Malik Rainer,Ewers Michael^ORCID,

Abstract

AbstractKlotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VShet was related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VShet carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VShet against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.

Funder

Alzheimer Forschung Initiative

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-021-23755-z.pdf

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