Evidence map›Paper›PMID 42163384›Full record

ArticleAlzheimer's research & therapy2026

A clinically feasible framework to estimate tau pathology and clinical-biological discordance in the Alzheimer's disease spectrum.

Jung-Lung Hsu, Shao-Yi Huang, Hsiu-Chuan Wu, Kun-Ju Lin, Kuo-Lun Huang, Chin-Chang Huang, SangYun Kim, Ing-Tsung Hsiao

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Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Jung-Lung HsuDepartment of Neurology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.
Shao-Yi HuangDepartment of Medical Imaging and Radiological Sciences, College of Medicine & Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
Hsiu-Chuan WuDepartment of Neurology, Linkou Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Kun-Ju LinDepartment of Medical Imaging and Radiological Sciences, College of Medicine & Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
Kuo-Lun HuangDepartment of Neurology, Linkou Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chin-Chang HuangDepartment of Neurology, Linkou Chang Gung Memorial Hospital & College of Medicine, Chang Gung University, Taoyuan, Taiwan.
SangYun KimDepartment of Neurology, Seoul National University College of Medicine & Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Ing-Tsung HsiaoDepartment of Medical Imaging and Radiological Sciences, College of Medicine & Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan. ihsiao@mail.cgu.edu.tw.

Funding

Chang Gung Memorial Hospital Research Fund CORPG3P0281, CORPG3P0291, BMRP488National Science and Technology Council MOST 111-2314-B-182A-036-MY2, NSTC 112-2628-B-182-007-MY3, NSTC-113-2314-B-182-042-MY2, NSTC-114-2314-B-182-043, NSTC 114-2314-B-182A-061-MY3
6 · The paper itself

Abstract

backgroundTau positron emission tomography (PET) is critical for biological staging and treatment stratification in Alzheimer's disease (AD), particularly in the era of anti-amyloid therapies where lower tau burden predicts greater clinical benefit. However, tau PET remains costly and inaccessible in many clinical settings. We aimed to develop and validate a clinically feasible framework to estimate global and regional tau burden using routinely available amyloid PET and clinical measures, aligned with the 2024 Alzheimer's Association (AA-2024) diagnostic framework, and to characterize clinical-biological discordance across the AD continuum.

methodsWe conducted a cross-sectional study of 229 individuals spanning cognitively unimpaired, mild cognitive impairment, and dementia stages who underwent [

resultsGlobal and regional tau burden increased stepwise across clinical severity and amyloid strata. High global tau burden was uncommon in individuals with CL 21-60 (6.1%) but increased in CL 61-100 (22.6%) and > 100 (36.2%). A multivariable model integrating CL, age, MMSE, and relative MTL volume demonstrated good discrimination for high global tau burden (AUC = 0.87) and neocortical involvement (AUC = 0.84). Model robustness was confirmed by bootstrap resampling. Among amyloid-positive participants, 53.1% exhibited clinical-predominant AD, characterized by older age and higher cardiovascular risk despite relatively modest tau burden, indicating substantial clinical-biological discordance.

conclusionRoutinely obtainable amyloid PET and clinical measures can approximate global and topographical tau burden with good accuracy and identify frequent clinical-biological discordance within the AD spectrum. This scalable framework provides a practical surrogate for tau PET in resource-limited settings and may support biological staging, therapeutic eligibility assessment, and precision treatment decision-making.

Indexed as

Alzheimer DiseaseBraintau ProteinsAgedAged, 80 and overCognitive DysfunctionCross-Sectional StudiesFemaleHumansMagnetic Resonance ImagingMalePositron-Emission Tomographytau ProteinsAlzheimer’s diseaseCardiovascular riskClinical–biological discordanceModel-based analysisTau PET

Identifiers

PMID42163384
PMCPMC13366714

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.