Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease-Reference-Cited by-同舟云学术

Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

Published:2023-09-01 Issue:9 Volume:80 Page:969
ISSN:2168-6149
Container-title:JAMA Neurology
language:en
Short-container-title:JAMA Neurol

Author:

Erickson Pontus¹,Simrén Joel¹²,Brum Wagner S.¹³,Ennis Gilda E.⁴⁵,Kollmorgen Gwendlyn⁶,Suridjan Ivonne⁶,Langhough Rebecca⁴⁵,Jonaitis Erin M.⁴⁵,Van Hulle Carol A.⁴⁵,Betthauser Tobey J.⁴⁵,Carlsson Cynthia M.⁴⁵⁷⁸,Asthana Sanjay⁴⁵⁷⁸,Ashton Nicholas J.¹⁹¹⁰¹¹,Johnson Sterling C.⁴⁵,Shaw Leslie M.¹²,Blennow Kaj¹²,Andreasson Ulf¹²,Bendlin Barbara B.⁴,Zetterberg Henrik¹²⁴¹³¹⁴,Weiner Michael¹⁵,Aisen Paul¹⁵,Petersen Ronald¹⁵,Jack Clifford R.¹⁵,Jagust William¹⁵,Trojanowki John Q¹⁵,Toga Arthur W.¹⁵,Beckett Laurel¹⁵,Green Robert C.¹⁵,Saykin Andrew J.¹⁵,Morris John¹⁵,Shaw Leslie M.¹⁵,Liu Enchi¹⁵,Montine Tom¹⁵,Thomas Ronald G.¹⁵,Donohue Michael¹⁵,Walter Sarah¹⁵,Gessert Devon¹⁵,Sather Tamie¹⁵,Jiminez Gus¹⁵,Harvey Danielle¹⁵,Bernstein Matthew¹⁵,Fox Nick¹⁵,Thompson Paul¹⁵,Schuff Norbert¹⁵,DeCArli Charles¹⁵,Borowski Bret¹⁵,Gunter Jeff¹⁵,Senjem Matt¹⁵,Vemuri Prashanthi¹⁵,Jones David¹⁵,Kantarci Kejal¹⁵,Ward Chad¹⁵,Koeppe Robert A.¹⁵,Foster Norm¹⁵,Reiman Eric M.¹⁵,Chen Kewei¹⁵,Mathis Chet¹⁵,Landau Susan¹⁵,Cairns Nigel J.¹⁵,Householder Erin¹⁵,Taylor Reinwald Lisa¹⁵,Lee Virginia¹⁵,Korecka Magdalena¹⁵,Figurski Michal¹⁵,Crawford Karen¹⁵,Neu Scott¹⁵,Foroud Tatiana M.¹⁵,Potkin Steven¹⁵,Shen Li¹⁵,Kelley Faber¹⁵,Kim Sungeun¹⁵,Nho Kwangsik¹⁵,Kachaturian Zaven¹⁵,Frank Richard¹⁵,J Snyder Peter J.¹⁵,Molchan Susan¹⁵,Kaye Jeffrey¹⁵,Quinn Joseph¹⁵,Lind Betty¹⁵,Carter Raina¹⁵,Dolen Sara¹⁵,Schneider Lon S.¹⁵,Pawluczyk Sonia¹⁵,Beccera Mauricio¹⁵,Teodoro Liberty¹⁵,M Spann Bryan M.¹⁵,Brewer James¹⁵,Vanderswag Helen¹⁵,Fleisher Adam¹⁵,Heidebrink Judith L¹⁵,Lord Joanne L¹⁵,Mason Sara¹⁵,Albers Colleen¹⁵,Knopman David¹⁵,Johnson Kris¹⁵,Doody Rachelle S¹⁵,Villanueva Meyer Javier¹⁵,Chowdhury Munir¹⁵,Rountree Susan¹⁵,Dang Mimi¹⁵,Stern Yaakov¹⁵,Honig Lawrence S¹⁵,Bell Karen L¹⁵,Ances Beau¹⁵,Morris John C¹⁵,Carroll Maria¹⁵,Leon Sue¹⁵,Mintun Mark A¹⁵,Schneider Stacy¹⁵,OliverNG Angela¹⁵,Griffith Randall¹⁵,Clark David¹⁵,Geldmacher David¹⁵,Brockington John¹⁵,Roberson Erik¹⁵,Grossman Hillel¹⁵,Mitsis Effie¹⁵,deToledo-Morrell Leyla¹⁵,Shah Raj C¹⁵,Duara Ranjan¹⁵,Varon Daniel¹⁵,Greig Maria T¹⁵,Roberts Peggy¹⁵,Albert Marilyn¹⁵,Onyike Chiadi¹⁵,D’Agostino Daniel¹⁵,Kielb Stephanie¹⁵,Galvin James E¹⁵,Pogorelec Dana M¹⁵,Cerbone Brittany¹⁵,Michel Christina A¹⁵,Rusinek Henry¹⁵,de Leon Mony J¹⁵,Glodzik Lidia¹⁵,De Santi Susan¹⁵,Murali Doraiswamy P¹⁵,R Petrella Jeffrey¹⁵,Z Wong Terence¹⁵,E Arnold Steven¹⁵,H Karlawish Jason¹⁵,Wolk David¹⁵,D Smith Charles¹⁵,Jicha Greg¹⁵,Hardy Peter¹⁵,Sinha Partha¹⁵,Oates Elizabeth¹⁵,Conrad Gary¹⁵,Lopez Oscar¹⁵,Oakley MaryAnn¹⁵,Simpson Donna¹⁵,Porsteinsson Anton¹⁵,Goldstein Bonnie¹⁵,Martin Kim¹⁵,Makino Kelly¹⁵,Saleem Ismail M¹⁵,Brand Connie¹⁵,Mulnard Ruth¹⁵,Thai Gaby¹⁵,Mc Adams Ortiz Catherine¹⁵,Womack Kyle¹⁵,Mathews Dana¹⁵,Quiceno Mary¹⁵,Diaz Arrastia Ramon¹⁵,King Richard¹⁵,Weiner Myron¹⁵,Martin Cook Kristen¹⁵,DeVous Michael¹⁵,Levey Allan¹⁵,Lah James¹⁵,Cellar Janet¹⁵,Burns Jeffrey¹⁵,Anderson Heather¹⁵,Swerdlow Russell¹⁵,Apostolova Liana¹⁵,Tingus Kathleen¹⁵,Woo Ellen¹⁵,Silverman Daniel¹⁵,Lu Po¹⁵,Bartzokis George¹⁵,Graff Radford Neill¹⁵,ParfittH Francine¹⁵,Kendall Tracy¹⁵,Johnson Heather¹⁵,Farlow Martin¹⁵,Marie Hake Ann¹⁵,Matthews Brandy¹⁵,Herring Scott¹⁵,Hunt Cynthia¹⁵,van Dyck Christopher¹⁵,Carson Richard¹⁵,MacAvoy Martha G¹⁵,Chertkow Howard¹⁵,Bergman Howard¹⁵,Hosein Chris¹⁵,Black Sandra¹⁵,Stefanovic Bojana¹⁵,Caldwell Curtis¹⁵,Yuek Robin Hsiung Ging¹⁵,Feldman Howard¹⁵,Mudge Benita¹⁵,Assaly Past Michele¹⁵,Kertesz Andrew¹⁵,Rogers John¹⁵,Trost Dick¹⁵,Bernick Charles¹⁵,Munic Donna¹⁵,Kerwin Diana¹⁵,Marsel Mesulam Marek¹⁵,Lipowski Kristine¹⁵,Kuo Wu Chuang¹⁵,Johnson Nancy¹⁵,Sadowsky Carl¹⁵,Martinez Walter¹⁵,Villena Teresa¹⁵,Scott Turner Raymond¹⁵,Johnson Kathleen¹⁵,Reynolds Brigid¹⁵,Sperling Reisa A¹⁵,Johnson Keith A¹⁵,Marshall Gad¹⁵,Frey Meghan¹⁵,Yesavage Jerome¹⁵,Taylor Joy L¹⁵,Lane Barton¹⁵,Rosen Allyson¹⁵,Tinklenberg Jared¹⁵,Sabbagh Marwan N¹⁵,Belden Christine M¹⁵,Jacobson Sandra A¹⁵,Sirrel Sherye A¹⁵,Kowall Neil¹⁵,Killiany Ronald¹⁵,Budson Andrew E¹⁵,Norbash Alexander¹⁵,Lynn Johnson Patricia¹⁵,Obisesan Thomas O¹⁵,Wolday Saba¹⁵,Allard Joanne¹⁵,Lerner Alan¹⁵,Ogrocki Paula¹⁵,Hudson Leon¹⁵,Fletcher Evan¹⁵,Carmichael Owen¹⁵,Olichney John¹⁵,DeCarli Charles¹⁵,Kittur Smita¹⁵,Borrie Michael¹⁵,Lee T Y¹⁵,Bartha Rob¹⁵,Johnson Sterling¹⁵,Asthana Sanjay¹⁵,Carlsson Cynthia M¹⁵,G Potkin Steven G¹⁵,Preda Adrian¹⁵,Nguyen Dana¹⁵,Tariot Pierre¹⁵,Reeder Stephanie¹⁵,Bates Vernice¹⁵,Capote Horacio¹⁵,Rainka Michelle¹⁵,Scharre Douglas W¹⁵,Kataki Maria¹⁵,Adeli Anahita¹⁵,Zimmerman Earl A¹⁵,Celmins Dzintra¹⁵,Brown Alice D¹⁵,Pearlson Godfrey D¹⁵,Blank Karen¹⁵,Anderson Karen¹⁵,Santulli Robert B¹⁵,Kitzmiller Tamar J¹⁵,Schwartz Eben S¹⁵,SinkS Kaycee M¹⁵,Williamson Jeff D¹⁵,Garg Pradeep¹⁵,Watkins Franklin¹⁵,Ott Brian R¹⁵,Querfurth Henry¹⁵,Tremont Geoffrey¹⁵,Salloway Stephen¹⁵,Malloy Paul¹⁵,Correia Stephen¹⁵,Rosen Howard J¹⁵,Miller Bruce L¹⁵,Mintzer Jacobo¹⁵,Spicer Kenneth¹⁵,Bachman David¹⁵,Finger Elizabether¹⁵,Pasternak Stephen¹⁵,Rachinsky Irina¹⁵,Drost Dick¹⁵,Pomara Nunzio¹⁵,Hernando Raymundo¹⁵,Sarrael Antero¹⁵,Schultz Susan K¹⁵,Boles Ponto Laura L¹⁵,Shim Hyungsub¹⁵,Elizabeth Smith Karen¹⁵,Relkin Norman¹⁵,Chaing Gloria¹⁵,Raudin Lisa¹⁵,Smith Amanda¹⁵,Fargher Kristin¹⁵,Ashok Raj Balebail¹⁵,

Affiliation:

1. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden

3. Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

4. School of Medicine and Public Health, University of Wisconsin-Madison, Madison

5. Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison

6. Roche Diagnostics GmbH, Penzberg, Germany

7. Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison

8. Geriatric Research Education and Clinical Center of the Wm. S. Middleton Memorial Veterans Hospital, Madison, Wisconsin

9. Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute, King’s College London, London, England

10. NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, England

11. Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway

12. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia

13. Institute of Neurology, Department of Neurodegenerative Disease, University College London, London, England

14. UK Dementia Research Institute, University College London, London, England

15. for the ADNI Cohort

Abstract

ImportanceKnowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid–negative, tau-positive (A−T+) cerebrospinal fluid (CSF) biomarker profile.ObjectiveTo estimate the prevalence of a CSF A−T+ biomarker profile and investigate its clinical implications.Design, Setting, and ParticipantsThis was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020). This was a multicenter study, with data collected from referral centers in clinical routine (UGOT) and research settings (ADNI and WISC). Eligible individuals had 1 lumbar puncture (all cohorts), 2 or more cognitive assessments (ADNI and WISC), and imaging (ADNI only) performed on 2 separate occasions. Data were analyzed on August 2022 to April 2023.ExposuresBaseline CSF Aβ42/40 and phosphorylated tau (p-tau)181; cognitive tests (ADNI: modified preclinical Alzheimer cognitive composite [mPACC]; WISC: modified 3-test PACC [PACC-3]). Exposures in the ADNI cohort included [18F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [18F]-flortaucipir, WISC: [18F]-MK6240).Main Outcomes and MeasuresPrimary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A−T+ vs A−T− groups. Secondary outcomes included cross-sectional tau-PET.ResultsA total of 7679 individuals (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) were included in the UGOT cohort, 970 individuals (mean [SD] age, 73 [7.0] years; 526 male [54%]) were included in the ADNI cohort, and 519 individuals (mean [SD] age, 60 [7.3] years; 346 female [67%]) were included in the WISC cohort. The prevalence of an A−T+ profile in the UGOT cohort was 4.1% (95% CI, 3.7%-4.6%), being less common than the other patterns. Longitudinally, no significant differences in rates of worsening were observed between A−T+ and A−T− profiles for cognition or imaging biomarkers. Cross-sectionally, A−T+ had similar tau-PET uptake to individuals with an A−T− biomarker profile.Conclusion and RelevanceResults suggest that the CSF A−T+ biomarker profile was found in approximately 5% of lumbar punctures and was not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals.

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

Link

https://jamanetwork.com/journals/jamaneurology/articlepdf/2807607/jamaneurology_erickson_2023_oi_230049_1694018374.34162.pdf

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