Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease
Por:
Salvadó, G, Janelidze, S, Bali, D, Dolado, AO, Therriault, J, Brum, WS, Binette, AP, Stomrud, E, Mattsson-Carlgren, N, Palmqvist, S, Coomans, EM, Teunissen, CE, van der Flier, WM, Rahmouni, N, Benzinger, TLS, Gispert, JD, Blennow, K, Dore, V, Feizpour, A, Rowe, CC, Alcolea, D, Fortea, J, Villeneuve, S, Johnson, SC, Rosa-Neto, P, Petersen, RC, Jack, CR, Schindler, SE, Suárez-Calvet, M, Ossenkoppele, R, Hansson, O
Publicada:
1 nov 2025
Ahead of Print:
1 sep 2025
Resumen:
IMPORTANCE Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid beta (A beta) pathology. OBJECTIVE To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying A beta status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (A beta positron emission tomography [PET] or cerebrospinal fluid [CSF]). DESIGN, SETTING, AND PARTICIPANTS This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET A beta biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). EXPOSURES Plasma p-tau217 levels measured by immunoassay. MAIN OUTCOME AND MEASURES A beta status, determined by CSF or A beta PET biomarkers. RESULTS Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were A beta positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE epsilon 4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 A beta-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true A beta-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). CONCLUSIONS AND RELEVANCE The findings highlight the potential of plasma p-tau217 as a stand-alone test-or when used in a sequential 2-step approach alongside PET or CSF testing-as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.
Filiaciones:
Salvadó, G:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Barcelonasseta Brain Res Ctr, Barcelona, Spain
Janelidze, S:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Bali, D:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Dolado, AO:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Therriault, J:
McGill Univ, McConnell Brain Imaging Ctr, Translat Neuroimaging Lab, Res Ctr Studies Aging, Montreal, PQ, Canada
McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
Brum, WS:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Molndal, Sweden
Univ Fed Rio Grande do Sul, Grad Program Biol Sci Biochem, Porto Alegre, Brazil
Binette, AP:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Stomrud, E:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Memory Clin, Malmo, Sweden
Mattsson-Carlgren, N:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Memory Clin, Malmo, Sweden
Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden
Palmqvist, S:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Memory Clin, Malmo, Sweden
Coomans, EM:
Vrije Univ, Amsterdam Univ Med Ctr, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Amsterdam Neurosci, Brain Imaging, Amsterdam, Netherlands
Teunissen, CE:
Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Neurochem Lab, Amsterdam, Netherlands
Amsterdam Neurosci, Neurodegenerat, Amsterdam, Netherlands
van der Flier, WM:
Vrije Univ, Amsterdam Univ Med Ctr, Alzheimer Ctr Amsterdam, Amsterdam, Netherlands
Amsterdam Neurosci, Neurodegenerat, Amsterdam, Netherlands
Amsterdam Univ Med Ctr, Epidemiol & Data Sci, Amsterdam, Netherlands
Rahmouni, N:
McGill Univ, McConnell Brain Imaging Ctr, Translat Neuroimaging Lab, Res Ctr Studies Aging, Montreal, PQ, Canada
McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
Benzinger, TLS:
Washington Univ, Sch Med, St Louis, MO USA
Knight Alzheimer Dis Res Ctr, St Louis, MO USA
Gispert, JD:
Barcelonasseta Brain Res Ctr, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Madrid, Spain
Univ Pompeu Fabra, Barcelona, Spain
Hosp Mar, Med Res Inst, Barcelona, Spain
Ctr Nacl Invest Cardiovasc, Madrid, Spain
Blennow, K:
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Gothenburg, Sweden
Sorbonne Univ, Pitie Salpetriere Hosp, Paris Brain Inst, ICM, Paris, France
Univ Sci & Technol China, Neurodegenerat Disorder Res Ctr, Div Life Sci & Med, Hefei, Peoples R China
Univ Sci & Technol China, Inst Aging & Brain Disorders, Dept Neurol, Hefei, Peoples R China
Univ Sci & Technol China, Affiliated Hosp 1, Hefei, Peoples R China
Dore, V:
Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia
CSIRO, Australian e Hlth Res Ctr, Melbourne, Vic, Australia
Feizpour, A:
Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia
Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia
Univ Melbourne, Florey Dept Neurosci & Mental Hlth, Melbourne, Vic, Australia
Rowe, CC:
Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia
Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia
Univ Melbourne, Florey Dept Neurosci & Mental Hlth, Melbourne, Vic, Australia
Alcolea, D:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Villeneuve, S:
Douglas Mental Hlth Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada
McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada
Johnson, SC:
Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI USA
Univ Wisconsin, Wisconsin Alzheimers Inst, Sch Med & Publ Hlth, Madison, WI USA
Rosa-Neto, P:
McGill Univ, McConnell Brain Imaging Ctr, Translat Neuroimaging Lab, Res Ctr Studies Aging, Montreal, PQ, Canada
McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada
Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada
Petersen, RC:
Mayo Clin, Dept Neurol, Rochester, MN USA
Jack, CR:
Mayo Clin, Dept Radiol, Rochester, MN USA
Schindler, SE:
Washington Univ, Sch Med, St Louis, MO USA
Knight Alzheimer Dis Res Ctr, St Louis, MO USA
Suárez-Calvet, M:
Barcelonasseta Brain Res Ctr, Barcelona, Spain
Hosp Mar, Med Res Inst, Barcelona, Spain
Hosp Mar, Serv Neurol, Barcelona, Spain
Ossenkoppele, R:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Amsterdam Neurosci, Neurodegenerat, Amsterdam, Netherlands
Amsterdam Univ Med Ctr, Alzheimer Ctr Amsterdam, Neurol, Amsterdam, Netherlands
Hansson, O:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Green Submitted, Green Published, hybrid
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