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Frequency and Clinical Outcomes Associated with Tau Positron Emission Tomography Positivity

Moscoso, Alexis ; Heeman, Fiona ; Raghavan, Sheelakumari ; Costoya-Sánchez, Alejandro ; Van Essen, Martijn ; Mainta, Ismini ; Camacho, Valle ; Rodríguez-Fonseca, Omar ; Silva-Rodríguez, Jesús and Perissinotti, Andrés , et al. (2025) In JAMA 334(3).
Abstract

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures: Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical... (More)

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures: Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration- and European Medicines Agency-approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures: Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results: Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET-positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET-positive/tau PET-negative (17% [95% CI, 13%-22%]) and Aβ PET-negative/tau PET-negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET-positive/tau PET-positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance: In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

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type
Contribution to journal
publication status
published
subject
in
JAMA
volume
334
issue
3
publisher
American Medical Association
external identifiers
  • pmid:40522652
  • scopus:105008812900
ISSN
0098-7484
DOI
10.1001/jama.2025.7817
language
English
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yes
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Publisher Copyright: © 2025 American Medical Association. All rights reserved, including those for text and data mining, AI training, and similar technologies.
id
5e1f7dc5-cb4e-45fd-8d5f-df9fa9d94266
date added to LUP
2026-01-29 15:46:42
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2026-01-30 07:21:05
@article{5e1f7dc5-cb4e-45fd-8d5f-df9fa9d94266,
  abstract     = {{<p>Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures: Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration- and European Medicines Agency-approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures: Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results: Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET-positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET-positive/tau PET-negative (17% [95% CI, 13%-22%]) and Aβ PET-negative/tau PET-negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET-positive/tau PET-positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance: In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.</p>}},
  author       = {{Moscoso, Alexis and Heeman, Fiona and Raghavan, Sheelakumari and Costoya-Sánchez, Alejandro and Van Essen, Martijn and Mainta, Ismini and Camacho, Valle and Rodríguez-Fonseca, Omar and Silva-Rodríguez, Jesús and Perissinotti, Andrés and Gu, Yuna and Yun, Jihwan and Peretti, Debora and Ribaldi, Federica and Coomans, Emma M. and Brum, Wagner S. and Grothe, Michel J. and Aguiar, Pablo and Bischof, Gérard N. and Drzezga, Alexander and Seo, Sang Won and Villeneuve, Sylvia and Malpetti, Maura and O'Brien, John T. and Rowe, James B. and Van De Giessen, Elsmarieke M. and Ossenkoppele, Rik and Jagust, William J. and Smith, Ruben and Hansson, Oskar and Frisoni, Giovanni B. and Garibotto, Valentina and Soleimani-Meigooni, David N. and Carrillo, Maria and Dickerson, Bradford C. and La Joie, Renaud and Rabinovici, Gil D. and Apostolova, Liana G. and Lamontagne, Pamela J. and Pontecorvo, Michael J. and Johnson, Keith A. and Sperling, Reisa A. and Weiner, Michael W. and Petersen, Ronald C. and Jack, Clifford R. and Vemuri, Prashanthi and Schöll, Michael}},
  issn         = {{0098-7484}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{3}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA}},
  title        = {{Frequency and Clinical Outcomes Associated with Tau Positron Emission Tomography Positivity}},
  url          = {{http://dx.doi.org/10.1001/jama.2025.7817}},
  doi          = {{10.1001/jama.2025.7817}},
  volume       = {{334}},
  year         = {{2025}},
}