A probabilistic framework for the diagnostic utility of tau-PET
(2025) In Alzheimer's & dementia : the journal of the Alzheimer's Association 21. p.106365-106365- Abstract
BACKGROUND: The tau-PET radiotracer [18F]flortaucipir enables in vivo detection of tau pathology in Alzheimer's Disease (AD) and has recently been FDA- and EMA-approved for clinical use. To support its implementation, we assessed tau-PET's positive predictive value (PPV) and negative predictive value (NPV) for clinico-pathological AD while accounting for age, amyloid-status, and pre-PET diagnostic certainty. METHOD: We computed the PPV and NPV of tau-PET using a formula that considers two types of false-positivity: clinico-pathological (positive tau-PET, yet tau does not significantly contribute to cognitive decline) and pathological (positive tau-PET, yet no/low tau is found at autopsy; Figure 1C). A systematic review yielded a... (More)
BACKGROUND: The tau-PET radiotracer [18F]flortaucipir enables in vivo detection of tau pathology in Alzheimer's Disease (AD) and has recently been FDA- and EMA-approved for clinical use. To support its implementation, we assessed tau-PET's positive predictive value (PPV) and negative predictive value (NPV) for clinico-pathological AD while accounting for age, amyloid-status, and pre-PET diagnostic certainty. METHOD: We computed the PPV and NPV of tau-PET using a formula that considers two types of false-positivity: clinico-pathological (positive tau-PET, yet tau does not significantly contribute to cognitive decline) and pathological (positive tau-PET, yet no/low tau is found at autopsy; Figure 1C). A systematic review yielded a weighted sensitivity of 93.6% and specificity of 83.9% for [18F]flortaucipir to detect postmortem Braak V/VI tau pathology (N = 349; Figure 1A). PPV and NPV were calculated across age groups using previously derived tau-PET positivity prevalence estimates in cognitively unimpaired individuals and hypothetical clinician-estimated prior probabilities of clinico-pathological AD (Figure 1B), resulting in the probability that cognitive impairment is primarily caused by AD-related tau pathology. We evaluated the PPV and NPV of tau-PET as a standalone biomarker and in combination with amyloid-PET. RESULT: The PPV of standalone tau-PET was highest in individuals with higher prior AD probabilities and younger ages (Figure 2A). For example, at a prior AD probability of 70%, the PPV for AD was 92% at ages 50-55, declining to 87% at ages 85-90. Tau-PET NPV was consistently high across ages and prior AD probabilities, effectively ruling out AD (Figure 2B). Obtaining tau-PET results after knowing amyloid-status markedly increased PPV for AD compared to both standalone tau-PET or amyloid-PET. The greatest increases in PPV from combining amyloid- and tau-PET, relative to amyloid-PET alone, occurred with lower pre-amyloid AD probabilities and older ages (up to a 37% increase; Figure 3A). Similarly, when tau-PET was obtained after amyloid-PET, strong increases in NPV were observed, particularly when prior AD probability was high (up to a 48% increase, Figure 3D). CONCLUSION: Tau-PET demonstrates high PPV and NPV for clinico-pathological AD as a standalone marker, with added diagnostic value when amyloid-status is already known. These findings underscore tau-PET's value for optimizing the diagnostic process.
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- author
- van Tol, Bastiaan G.J. ; Groot, Colin LU ; van de Giessen, Elsmarieke ; Pijnenburg, Yolande A.L. ; Coomans, Emma M. LU and Ossenkoppele, Rik LU
- organization
- publishing date
- 2025-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Alzheimer's & dementia : the journal of the Alzheimer's Association
- volume
- 21
- pages
- 106365 - 106365
- publisher
- Wiley
- external identifiers
-
- scopus:105027034231
- pmid:41513597
- ISSN
- 1552-5279
- DOI
- 10.1002/alz70856_106365
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
- id
- 6fa12bec-8978-493d-bdbb-5cdce0564d2e
- date added to LUP
- 2026-02-12 15:08:34
- date last changed
- 2026-02-12 15:58:43
@misc{6fa12bec-8978-493d-bdbb-5cdce0564d2e,
abstract = {{<p>BACKGROUND: The tau-PET radiotracer [18F]flortaucipir enables in vivo detection of tau pathology in Alzheimer's Disease (AD) and has recently been FDA- and EMA-approved for clinical use. To support its implementation, we assessed tau-PET's positive predictive value (PPV) and negative predictive value (NPV) for clinico-pathological AD while accounting for age, amyloid-status, and pre-PET diagnostic certainty. METHOD: We computed the PPV and NPV of tau-PET using a formula that considers two types of false-positivity: clinico-pathological (positive tau-PET, yet tau does not significantly contribute to cognitive decline) and pathological (positive tau-PET, yet no/low tau is found at autopsy; Figure 1C). A systematic review yielded a weighted sensitivity of 93.6% and specificity of 83.9% for [18F]flortaucipir to detect postmortem Braak V/VI tau pathology (N = 349; Figure 1A). PPV and NPV were calculated across age groups using previously derived tau-PET positivity prevalence estimates in cognitively unimpaired individuals and hypothetical clinician-estimated prior probabilities of clinico-pathological AD (Figure 1B), resulting in the probability that cognitive impairment is primarily caused by AD-related tau pathology. We evaluated the PPV and NPV of tau-PET as a standalone biomarker and in combination with amyloid-PET. RESULT: The PPV of standalone tau-PET was highest in individuals with higher prior AD probabilities and younger ages (Figure 2A). For example, at a prior AD probability of 70%, the PPV for AD was 92% at ages 50-55, declining to 87% at ages 85-90. Tau-PET NPV was consistently high across ages and prior AD probabilities, effectively ruling out AD (Figure 2B). Obtaining tau-PET results after knowing amyloid-status markedly increased PPV for AD compared to both standalone tau-PET or amyloid-PET. The greatest increases in PPV from combining amyloid- and tau-PET, relative to amyloid-PET alone, occurred with lower pre-amyloid AD probabilities and older ages (up to a 37% increase; Figure 3A). Similarly, when tau-PET was obtained after amyloid-PET, strong increases in NPV were observed, particularly when prior AD probability was high (up to a 48% increase, Figure 3D). CONCLUSION: Tau-PET demonstrates high PPV and NPV for clinico-pathological AD as a standalone marker, with added diagnostic value when amyloid-status is already known. These findings underscore tau-PET's value for optimizing the diagnostic process.</p>}},
author = {{van Tol, Bastiaan G.J. and Groot, Colin and van de Giessen, Elsmarieke and Pijnenburg, Yolande A.L. and Coomans, Emma M. and Ossenkoppele, Rik}},
issn = {{1552-5279}},
language = {{eng}},
month = {{12}},
note = {{Conference Abstract}},
pages = {{106365--106365}},
publisher = {{Wiley}},
series = {{Alzheimer's & dementia : the journal of the Alzheimer's Association}},
title = {{A probabilistic framework for the diagnostic utility of tau-PET}},
url = {{http://dx.doi.org/10.1002/alz70856_106365}},
doi = {{10.1002/alz70856_106365}},
volume = {{21}},
year = {{2025}},
}