Integrating MRI Volume and Plasma p-Tau217 for Amyloid Risk Stratification in Early-Stage Alzheimer Disease
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND OBJECTIVES: Identifying β-amyloid (Aβ) positivity is crucial for selecting candidates for Aβ-targeted therapies in early-stage Alzheimer disease (AD). While Aβ PET is accurate, its high cost limits routine use. Plasma p-tau217 testing offers a less invasive option but also incurs additional costs. Structural brain MRI, routinely used in cognitive assessments, can identify features predictive of Aβ positivity without extra expense. We evaluated a 2-stage workflow integrating MRI-based features and plasma p-tau217 to efficiently predict Aβ PET positivity in early-stage AD. METHODS: This prospective cohort study included participants with mild cognitive impairment (MCI) or early Alzheimer-type dementia (ATD) from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD; Korea) and Alzheimer's Disease Neuroimaging Initiative (ADNI; US) cohorts. Eligible participants had a Clinical Dementia Rating score of 0.5, along with MRI, plasma p-tau217, and Aβ PET data. A random forest classifier predicting Aβ PET positivity was developed using MRI-based brain atrophy patterns and APOE ε4 status. Participants were stratified into low-risk, intermediate-risk, and high-risk groups; plasma p-tau217 testing was performed only in intermediate-risk individuals. Outcomes included positive predictive value (PPV), negative predictive value (NPV), and overall accuracy. RESULTS: A total of 807 K-ROAD participants (median age 72.0 years, 58.7% female) and 230 ADNI participants (median age 70.9 years, 49.1% female) were analyzed. Using a 95% sensitivity/specificity strategy, the low-risk group demonstrated NPVs of 94.7% (91.7%-97.7%, K-ROAD) and 99.0% (97.0%-100.0%, ADNI). The high-risk group showed PPVs of 97.6% (95.9%-99.3%, K-ROAD) and 98.8% (96.5%-100.0%, ADNI). Intermediate-risk groups comprised 33.3% (K-ROAD) and 20.9% (ADNI) of participants. Plasma p-tau217 testing in intermediate-risk groups yielded PPVs of 92.5% (88.7%-96.3%, K-ROAD) and 90.0% (79.0%-100.0%, ADNI) and NPVs of 83.1% (75.0%-91.2%, K-ROAD) and 83.3% (66.1%-100.0%, ADNI). The overall workflow accuracy was 94.2% (92.6%-95.8%, K-ROAD) and 96.5% (94.1%-98.9%, ADNI). DISCUSSION: The 2-stage diagnostic workflow integrating MRI-based risk stratification and plasma p-tau217 testing accurately identified individuals with Aβ PET positivity in early-stage AD, substantially reducing the need for additional biomarker testing. However, the generalizability may be limited by modest incremental improvement over baseline models and limited racial and ethnic diversity.
Source: Neurology
Authors: Sohyun Yim, Seongbeom Park, Kyoungyoon Lim, Heekyung Kang, Daeun Shin, Hyunjin Jo, Hyemin Jang, Michael W. Weiner, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Sung Hoon Kang, Jihwan Yun, Min Young Chun, Eun-Joo Kim, Hee Jin Kim, Duk L. Na, Jun Pyo Kim, Sang Won Seo, Kichang Kwak, for the K-ROAD study and the Alzheimer's Disease Neuroimaging Initiative
Institutions: Samsung Medical Center, Sungkyunkwan University, Seoul National University, Seoul National University Hospital, University of California, San Francisco, University of Wisconsin–Madison, Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg, University of Science and Technology of China, Sorbonne Université, Pitié-Salpêtrière Hospital, Institut du Cerveau, King's College London, Stavanger University Hospital, Korea University Guro Hospital, Kyung Hee University, Yonsei University, Yonsei University Health System, Yongin Severance Hospital, Pusan National University Hospital, Pusan National University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Eli Lilly and Company, Biogen, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, Prothena, National Institute for Health and Care Research, University College London, European Commission, National Research Foundation, Korea Health Industry Development Institute, National Research Foundation of Korea, Hjärnfonden, Novo Nordisk, Vetenskapsrådet, Siemens Healthineers, Ministry of Science and ICT, South Korea, UK Dementia Research Institute, Samsung, HORIZON EUROPE Framework Programme, Korea National Institute of Health, Institute for Information and Communications Technology Promotion
Awards: G1057200632, G1153927585, G1307999793, G1343867371, G1346957673, G1451011034, G1451607819, G150733400, G1546555014, G1551449788, G1588116593, G1710774808, G1771944843, G1802301745, G1833008592, G1928552717, G1938858119, G196098375, G201353144, G2057385626, G2081597990, G2157144545, G2224941001, G2237966762, G2256555670, G237833635, G2434909840, G2475953241, G2543812357, G2756832787, G2799940023, G2804859505, G292763017, G3241251457, Fluid biomarkers for neurodegenerative dementias, G3509189227, G3791011679, G3809224024, G3842727039, G3903502641, G3914690605, G4166693258, G4228906844, G4234328627, G4244943609, G4260843567, G4288937912, G432431387, G4377393254, G4700831490, G4786159458, G490925689, G4960203590, G5040492720, G506008078, G516766298, G5264190596, Fluid biomarkers for neurodegenerative dementias, G5576250680, G5712520100, G5778058681, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6207287561, G6252389079, G6289970089, G6361952146, G6544145387, G6647163617, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6701856265, G6745400708, G691317373, G7075164165, G7293611571, G7699972493, G7907773732, G7972240148, G839602194, G8782684654
OpenAlex ID: W4413316423