Scholarlink

<p>Detection of Alzheimer’s disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood–brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in classifying AD based on biomarker-confirmed (amyloid-β and Tau) status and replicated in independent samples from the Knight-Alzheimer Disease Research Center (<i>n</i> = 551: 76 AD, 475 cognitively unimpaired) and preclinical A4 (<i>n</i> = 1,767) cohorts. Classification of biomarker-confirmed status by blood circRNAs (area under the curve (AUC) = 0.945) had a higher predictive ability than plasma pTau217 (AUC = 0.877) and was further improved in the integrated model (circRNA+pTau217 AUC = 0.977). This model showed high AD specificity with low predictive power for Parkinson’s disease, frontotemporal dementia, and other neurodegenerative diseases. In the Knight-Alzheimer Disease Research Center discovery cohort, these circRNAs (hazard ratio = 2.92) outperformed pTau217 (hazard ratio = 1.81) and amyloid-positron emission tomography when predicting progression to symptomatic AD. Although prospective validation in larger cohorts is needed, these results propose blood circRNAs as potential biomarkers for AD diagnosis and disease progression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Blood-based circular RNAs for early diagnosis of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月1日

查看全文
  • Bridget Phillips,
  • Jessie Sanford,
  • Vaibhav A. Janve,
  • Menghan Liu,
  • Matt Johnson,
  • Katherine Gong,
  • Kristy Bergmann,
  • Joseph Lowery,
  • Allison Flynn,
  • William Brock,
  • Brenda Sanchez Montejo,
  • Nicholas Sykora,
  • John Budde,
  • Nikolaos Mellios,
  • Grigorios Papageorgiou,
  • Reisa A. Sperling,
  • Rachel F. Buckley,
  • Mabel Seto,
  • John C. Morris,
  • Joel S. Perlmutter,
  • Paul T. Kotzbauer,
  • Richard J. Perrin,
  • Timothy J. Hohman,
  • Laura Ibanez,
  • Carlos Cruchaga

摘要

Detection of Alzheimer’s disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood–brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in classifying AD based on biomarker-confirmed (amyloid-β and Tau) status and replicated in independent samples from the Knight-Alzheimer Disease Research Center (n = 551: 76 AD, 475 cognitively unimpaired) and preclinical A4 (n = 1,767) cohorts. Classification of biomarker-confirmed status by blood circRNAs (area under the curve (AUC) = 0.945) had a higher predictive ability than plasma pTau217 (AUC = 0.877) and was further improved in the integrated model (circRNA+pTau217 AUC = 0.977). This model showed high AD specificity with low predictive power for Parkinson’s disease, frontotemporal dementia, and other neurodegenerative diseases. In the Knight-Alzheimer Disease Research Center discovery cohort, these circRNAs (hazard ratio = 2.92) outperformed pTau217 (hazard ratio = 1.81) and amyloid-positron emission tomography when predicting progression to symptomatic AD. Although prospective validation in larger cohorts is needed, these results propose blood circRNAs as potential biomarkers for AD diagnosis and disease progression.