CT-derived brain volumes and plasma p-Tau217 for risk stratification of amyloid positivity in early-stage Alzheimer’s disease

Year: 2025

Type: article

Abstract: BACKGROUND: Early detection of amyloid-β (Aβ) pathology is critical for timely intervention in Alzheimer's disease (AD). While Aβ positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers are accurate, their high cost and limited accessibility hinder routine use. We developed a computed tomography (CT)-based, two-stage workflow combining CT-derived atrophy patterns with plasma phosphorylated tau 217 (p-Tau217) to predict Aβ PET positivity. METHODS: In this cohort of 616 participants (521 with mild cognitive impairment (MCI], 95 with early dementia of Alzheimer's type (DAT]; age 60-93 years), CT, p-Tau217 assays, and Aβ PET were performed. A random forest model incorporating CT-derived regional W-scores and apolipoprotein E ε4 (APOE ε4) status stratified individuals into low-, intermediate-, and high-risk groups. p-Tau217 testing was reserved for the intermediate-risk group. RESULTS: At a 95% sensitivity/specificity threshold, CT-based stratification yielded a low-risk negative predictive value (NPV) of 95.8% (93.0-98.6%) and a high-risk positive predictive value (PPV) of 98.4% (96.8-100.0%), with 28.2% classified as intermediate-risk. Targeted plasma testing of intermediate-risk group improved the overall PPV to 92.8% (88.5-97.1%) and the overall NPV to 88.9% (78.6-99.2%), achieving an overall accuracy of 95.8% (94.2-97.4%). The CT-based workflow's accuracy was non-inferior to our MRI-based method (area under the curve 0.96 vs. 0.95; p = 0.14). CONCLUSIONS: This CT-based, two-stage approach is a cost-effective, scalable alternative to MRI-based strategies, leveraging routine CT and selective p-Tau217 testing to enhance early AD detection and optimize resource utilization in clinical practice.

Source: Alzheimer s Research & Therapy

DOI: 10.1186/s13195-025-01870-z

Authors: Sohyun Yim, Seongbeom Park, Kyoung Yoon Lim, Heekyoung Kang, Daeun Shin, Hyemin Jang, Michael Weiner, Henrik Zetterberg, Kaj Blennow, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Sung Hoon Kang, Jihwan Yun, Minyoung Chun, Eunjoo Kim, Heejin Kim, Duk L. Na, Jun Pyo Kim, Sang Won Seo, Kichang Kwak, K-ROAD study

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, Institut des Sciences Moléculaires, Pitié-Salpêtrière Hospital, Institut du Cerveau, King's College London, South London and Maudsley NHS Foundation Trust, Stavanger University Hospital, Korea University Guro Hospital, Kyung Hee University, Kyung Hee University Medical Center, Yonsei University, Yonsei University Health System, Yongin Severance Hospital, Pusan National University Hospital, Pusan National University

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,290

OpenAlex ID: W4415616135