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<p>Plasma phosphorylated-tau (p-tau) biomarkers show high performance as first-in-line tests in the evaluation of patients with cognitive symptoms and have also found utility in clinical trials for anti-amyloid drug therapies for Alzheimer’s disease (AD). Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (Aβ) pathology in CU individuals with brain amyloidosis from CSF Aβ42/40 ratio (<i>n</i> = 317) or Aβ PET scans (<i>n</i> = 277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF Aβ + participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low Aβ burden (CSF Aβ-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in Aβ PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.</p>

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Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月25日

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  • Przemysław R. Kac,
  • Armand González-Escalante,
  • Marta Milà-Alomà,
  • Nicholas J. Ashton,
  • Mahnaz Shekari,
  • Paula Ortiz-Romero,
  • Michael Turton,
  • Peter Harrison,
  • Henrik Zetterberg,
  • Juan Domingo Gispert,
  • Thomas K. Karikari,
  • Marc Suárez-Calvet,
  • Kaj Blennow

摘要

Plasma phosphorylated-tau (p-tau) biomarkers show high performance as first-in-line tests in the evaluation of patients with cognitive symptoms and have also found utility in clinical trials for anti-amyloid drug therapies for Alzheimer’s disease (AD). Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (Aβ) pathology in CU individuals with brain amyloidosis from CSF Aβ42/40 ratio (n = 317) or Aβ PET scans (n = 277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF Aβ + participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low Aβ burden (CSF Aβ-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in Aβ PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.