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<p>Accurately predicting disease progression remains a major challenge in Alzheimer’s disease (AD). Here we show that a biomarker-integrated prognostic staging system can stratify progression risk across the disease course by jointly incorporating cognitive status, established risk factors, plasma biomarkers, and neuroimaging measures. In the K-ROAD cohort (<i>N</i> = 1,263), the dominant prognostic contributors varied by clinical context—GFAP in cognitively unimpaired individuals, hippocampal volume in mild cognitive impairment, and age in dementia—while plasma phosphorylated tau-217 provided consistent secondary prognostic information across stages. Outcome-specific staging captured clinically meaningful gradients of progression risk and informed construction of a unified six-stage framework (Stage 0–IVB) with distinct inflection points of accelerated decline. External validation in the ADNI cohort (<i>N</i> = 290) demonstrated consistent patterns of worsening prognosis, particularly in early and intermediate stages. This system provides a clinically interpretable approach to risk stratification and may serve as an exploratory framework for biomarker-integrated prognostic stratification in AD.</p>

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Biomarker-integrated prognostic stagings for Alzheimer’s Disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Daeun Shin,
  • Sungjoo Lee,
  • Jun Pyo Kim,
  • Hyemin Jang,
  • Jihwan Yun,
  • Min Young Chun,
  • Jehyun Ahn,
  • Seongmi Kim,
  • Kyoungmin Kim,
  • Soyeon Yoon,
  • Hee Jin Kim,
  • Heekyoung Kang,
  • Sohyun Yim,
  • Hee Kyung Park,
  • Seonghyeon Kim,
  • Duk L. Na,
  • Henrik Zetterberg,
  • Kaj Blennow,
  • Fernando Gonzalez-Ortiz,
  • Nicholas J. Ashton,
  • Michael W. Weiner,
  • Sang Won Seo,
  • Kyunga Kim

摘要

Accurately predicting disease progression remains a major challenge in Alzheimer’s disease (AD). Here we show that a biomarker-integrated prognostic staging system can stratify progression risk across the disease course by jointly incorporating cognitive status, established risk factors, plasma biomarkers, and neuroimaging measures. In the K-ROAD cohort (N = 1,263), the dominant prognostic contributors varied by clinical context—GFAP in cognitively unimpaired individuals, hippocampal volume in mild cognitive impairment, and age in dementia—while plasma phosphorylated tau-217 provided consistent secondary prognostic information across stages. Outcome-specific staging captured clinically meaningful gradients of progression risk and informed construction of a unified six-stage framework (Stage 0–IVB) with distinct inflection points of accelerated decline. External validation in the ADNI cohort (N = 290) demonstrated consistent patterns of worsening prognosis, particularly in early and intermediate stages. This system provides a clinically interpretable approach to risk stratification and may serve as an exploratory framework for biomarker-integrated prognostic stratification in AD.