Comparison of Plasma p-tau217 and [18F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia

被引：2

作者：

Quispialaya, Kely Monica ^{[1
,2
,3
]}

Therriault, Joseph ^{[1
,3
,4
]}

Aliaga, Antonio ^{[1
,2
,5
]}

Benedet, Andrea L. ^{[6
]}

Ashton, Nicholas J. ^{[6
,7
]}

Karikari, Thomas ^{[6
,8
]}

Cassa Macedo, Arthur ^{[1
,3
,4
]}

Rahmouni, Nesrine ^{[1
,3
,4
]}

Tissot, Cecile ^{[1
,4
,9
]}

Fernandez Arias, Jaime ^{[1
,3
,4
]}

Wang, Yi-Ting Tina ^{[1
,3
,4
]}

Trudel, Lydia ^{[1
,3
,4
]}

Hosseini, Seyyed Ali ^{[1
,3
,4
]}

Matsudaira, Takashi ^{[10
,11
]}

Chan, Tevy ^{[1
,2
,3
]}

Pascoal, Tharick ^{[8
]}

Gilfix, Brian ^{[12
]}

Vitali, Paolo ^{[1
]}

Zimmer, Eduardo R. ^{[1
,5
,13
,14
]}

Provost, Karine ^{[15
]}

Soucy, Jean-Paul ^{[3
,15
]}

Gauthier, Serge ^{[1
,4
,16
]}

Zetterberg, Henrik ^{[6
,17
,18
,19
,20
,21
]}

Jean-Claude, Bertrand J. ^{[2
]}

Blennow, Kaj ^{[6
,17
]}

Rosa-Neto, Pedro ^{[1
,2
,3
,4
,16
]}

机构：

[1] McGill Univ, Res Ctr Studies Aging, Montreal Neurol Inst, McConnell Brain Imaging Ctr,Translat Neuroimaging, Montreal, PQ, Canada

[2] McGill Univ, Dept Expt Med, Montreal, PQ, Canada

[3] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada

[4] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada

[5] Univ Fed Rio Grande do Sul, Grad Program Biol Sci Biochem PPGBioq & Pharmacol, Porto Alegre, Brazil

[6] Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal, Sweden

[7] Univ Gothenburg, Wallenberg Ctr Mol Med, Gothenburg, Sweden

[8] Univ Pittsburgh, Dept Neurol & Psychiat, Sch Med, Pittsburgh, PA USA

[9] Lawrence Berkeley Natl Lab, Berkeley, CA USA

[10] Hamamatsu Univ Sch Med, Dept Biofunct Imaging, Hamamatsu, Shizuoka, Japan

[11] NHO Shizuoka Inst Epilepsy & Neurol Disorders, Dept Neurol, Shizuoka, Japan

[12] McGill Univ, Dept Specialized Med, Montreal, PQ, Canada

[13] Univ Fed Rio Grande do Sul, Dept Pharmacol, Porto Alegre, Brazil

[14] Pontif Catholic Univ Rio Grande do Sul, Brain Inst Rio Grande do Sul, Porto Alegre, Brazil

[15] Ctr Hosp Univ Montreal, Montreal, PQ, Canada

[16] McGill Univ, Dept Psychiat, Montreal, PQ, Canada

[17] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[18] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England

[19] UCL, UK Dementia Res Inst, London, England

[20] Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China

[21] Univ Wisconsin, Univ Wisconsin Madison, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI USA

来源：

NEUROLOGY | 2025年 / 104卷 / 02期

基金：

加拿大健康研究院;

关键词：

NATIONAL INSTITUTE; DIAGNOSIS; PET; ASSOCIATION;

D O I：

10.1212/WNL.0000000000210211

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Objectives To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [F-18]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments. Methods We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (A beta 42, p-tau181, and total tau levels), as well as [F-18]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications. To determine whether the [F-18]FDG-PET images were compatible with AD, images were visually rated by 2 nuclear medicine experts. Using a contingency analysis, we evaluated the accuracy of [F-18]FDG-PET scan interpretation and plasma p-tau217 for an AD biomarker profile in CSF and for amyloid-PET positivity. Results A total of 81 individuals with early onset and/or atypical dementia were included in this study (mean age = 65 years; 48/81 female (59%). Both [F-18]FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers ([F-18]FDG-PET area under the curve [AUC]: 71%; plasma p-tau217 AUC: 81%). Although both biomarkers had similar specificity for AD [F-18]FDG-PET: 70%, CI: 0.56-0.81; plasma p-tau217: 70%, CI: 0.56-0.81), plasma p-tau217 had higher sensitivity for AD (plasma p-tau217: 97%, CI: 0.85-0.99 vs [F-18]FDG-PET: 73%, CI: 0.57-0.85) (p = 0.01). Overall accuracy was also higher for plasma p-tau217 (AUC = 84%, CI: 0.75-0.93 vs 72%, CI: 0.60-0.83 of [F-18]FDG-PET) (p = 0.02). The same pattern of results was observed when using amyloid-PET as the reference standard. Discussion Our study provides evidence that plasma p-tau217 has strong discriminative accuracy for AD among patients with early-onset and/or atypical dementia assessed in specialized settings. Future work should replicate these findings in secondary care settings.

引用

页数：11

共 50 条

[1] Focal cortical presentations of Alzheimer's disease [J].

Alladi, S. ;

Xuereb, J. ;

Bak, T. ;

Nestor, P. ;

Knibb, J. ;

Patterson, K. ;

Hodges, J. R. .

BRAIN, 2007, 130 :2636-2645

[2] Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology [J].

Ashton, Nicholas J. ;

Brum, Wagner S. ;

Di Molfetta, Guglielmo ;

Benedet, Andrea L. ;

Arslan, Burak ;

Jonaitis, Erin ;

Langhough, Rebecca E. ;

Cody, Karly ;

Wilson, Rachael ;

Carlsson, Cynthia M. ;

Vanmechelen, Eugeen ;

Montoliu-Gaya, Laia ;

Lantero-Rodriguez, Juan ;

Rahmouni, Nesrine ;

Tissot, Cecile ;

Stevenson, Jenna ;

Servaes, Stijn ;

Therriault, Joseph ;

Pascoal, Tharick ;

Lleo, Alberto ;

Alcolea, Daniel ;

Fortea, Juan ;

Rosa-Neto, Pedro ;

Johnson, Sterling ;

Jeromin, Andreas ;

Blennow, Kaj ;

Zetterberg, Henrik .

JAMA NEUROLOGY, 2024, 81 (03) :255-263

[3] Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease [J].

Bateman, Randall J. ;

Xiong, Chengjie ;

Benzinger, Tammie L. S. ;

Fagan, Anne M. ;

Goate, Alison ;

Fox, Nick C. ;

Marcus, Daniel S. ;

Cairns, Nigel J. ;

Xie, Xianyun ;

Blazey, Tyler M. ;

Holtzman, David M. ;

Santacruz, Anna ;

Buckles, Virginia ;

Oliver, Angela ;

Moulder, Krista ;

Aisen, Paul S. ;

Ghetti, Bernardino ;

Klunk, William E. ;

McDade, Eric ;

Martins, Ralph N. ;

Masters, Colin L. ;

Mayeux, Richard ;

Ringman, John M. ;

Rossor, Martin N. ;

Schofield, Peter R. ;

Sperling, Reisa A. ;

Salloway, Stephen ;

Morris, John C. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (09) :795-804

[4] Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010 [J].

Beach, Thomas G. ;

Monsell, Sarah E. ;

Phillips, Leslie E. ;

Kukull, Walter .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2012, 71 (04) :266-273

[5] FDG-PET in tau-negative amnestic dementia resembles that of autopsy-proven hippocampal sclerosis [J].

Botha, Hugo ;

Mantyh, William G. ;

Murray, Melissa E. ;

Knopman, David S. ;

Przybelski, Scott A. ;

Wiste, Heather J. ;

Graff-Radford, Jonathan ;

Josephs, Keith A. ;

Schwarz, Christopher G. ;

Kremers, Walter K. ;

Boeve, Bradley F. ;

Petersen, Ronald C. ;

Machulda, Mary M. ;

Parisi, Joseph E. ;

Dickson, Dennis W. ;

Lowe, Val ;

Jack, Clifford R., Jr. ;

Jones, David T. .

BRAIN, 2018, 141 :1201-1217

[6] A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases [J].

Brum, Wagner S. ;

Cullen, Nicholas C. ;

Janelidze, Shorena ;

Ashton, Nicholas J. ;

Zimmer, Eduardo R. ;

Therriault, Joseph ;

Benedet, Andrea L. ;

Rahmouni, Nesrine ;

Tissot, Cecile ;

Stevenson, Jenna ;

Servaes, Stijn ;

Triana-Baltzer, Gallen ;

Kolb, Hartmuth C. ;

Palmqvist, Sebastian ;

Stomrud, Erik ;

Rosa-Neto, Pedro ;

Blennow, Kaj ;

Hansson, Oskar .

NATURE AGING, 2023, 3 (09) :1079-+

[7] Amyloid-PET and 18F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias [J].

Chetelat, Gael ;

Arbizu, Javier ;

Barthel, Henryk ;

Garibotto, Valentina ;

Law, Ian ;

Morbelli, Silvia ;

van de Giessen, Elsmarieke ;

Agosta, Federica ;

Barkhof, Frederik ;

Brooks, David J. ;

Carrillo, Maria C. ;

Dubois, Bruno ;

Fjell, Anders M. ;

Frisoni, Giovanni B. ;

Hansson, Oskar ;

Herholz, Karl ;

Hutton, Brian F. ;

Jack, Clifford R., Jr. ;

Lammertsma, Adriaan A. ;

Landau, Susan M. ;

Minoshima, Satoshi ;

Nobili, Flavio ;

Nordberg, Agneta ;

Ossenkoppele, Rik ;

Oyen, Wim J. G. ;

Perani, Daniela ;

Rabinovici, Gil D. ;

Scheltens, Philip ;

Villemagne, Victor L. ;

Zetterberg, Henrik ;

Drzezga, Alexander .

LANCET NEUROLOGY, 2020, 19 (11) :951-962

[8] Lecanemab: Appropriate Use Recommendations [J].

Cummings, J. ;

Apostolova, L. ;

Rabinovici, G. D. ;

Atri, A. ;

Aisen, P. ;

Greenberg, S. ;

Hendrix, S. ;

Selkoe, D. ;

Weiner, M. ;

Petersen, R. C. ;

Salloway, S. .

JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, 2023, 10 (03) :362-377

[9] COMPARING THE AREAS UNDER 2 OR MORE CORRELATED RECEIVER OPERATING CHARACTERISTIC CURVES - A NONPARAMETRIC APPROACH [J].

DELONG, ER ;

DELONG, DM ;

CLARKEPEARSON, DI .

BIOMETRICS, 1988, 44 (03) :837-845

[10] Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies [J].

Diaz-Galvan, Patricia ;

Przybelski, Scott A. ;

Algeciras-Schimnich, Alicia ;

Figdore, Dan J. ;

Lesnick, Timothy G. ;

Schwarz, Christopher G. ;

Senjem, Matthew L. ;

Gunter, Jeffrey L. ;

Jack, Clifford R., Jr. ;

Hmin, Paul ;

Jain, Manoj K. ;

Miyagawa, Toji ;

Forsberg, Leah K. ;

Fields, Julie A. ;

Savica, Rodolfo ;

Graff-Radford, Jonathan ;

Ramanan, Vijay K. ;

Jones, David T. ;

Botha, Hugo ;

St Louis, Erik K. ;

Knopman, David S. ;

Graff-Radford, Neill R. ;

Ferman, Tanis J. ;

Petersen, Ronald C. ;

Lowe, Val J. ;

Boeve, Bradley F. ;

Kantarci, Kejal .

ALZHEIMERS & DEMENTIA, 2024, 20 (04) :2485-2496

← 1 2 3 4 5 →