Scholarlink

Background <p>Plasma phosphorylated Tau217 (pTau217) represents a sensitive blood-based biomarker for Alzheimer’s disease (AD). This study investigated the performance of plasma pTau217 alone and as a composite score (Aβ1-40/Aβ1-42*pTau217) for detecting low Aβ1-42/1-40 in cerebrospinal fluid (CSF) as a surrogate marker of brain β-amyloid pathological changes.</p> Methods <p>We analysed plasma samples from 82 pre-selected participants who were dichotomized according to their CSF Aβ42/40 ratio after data-driven cutoff determination by Gaussian mixture modelling. The study cohort included patients in very early disease stages with mild cognitive impairment (MCI) due to AD and mild dementia due to AD in the Aβ-positive group and MCI due to other causes and mild dementia due to other causes in the Aβ-negative group. Concentrations of plasma pTau181 and pTau217 were determined on the fully automated LUMIPULSE platform. Additionally, plasma Aβ1-42/1-40 and pTau217 were assessed after consecutive Aβ- and Tau-immunoprecipitations (IPs). Corrections for age and sex effects in primary variables were done using a multivariate linear model on a logarithmic scale. Results are reported using both adjusted and unadjusted values.</p> Results <p>After adjustment for age and sex, median plasma pTau217 was increased by 203% in participants with low CSF Aβ1-42/1-40 (i.e. Aβ-positive), while pTau181 was increased by only 61%. PTau217 showed a larger area under the receiver operating characteristics curve (AUC) of 0.88 in identifying Aβ-positive individuals compared to plasma pTau181 (AUC: 0.78). Plasma Aβ1-42/1-40 ratio in Aβ-IP eluates (adjusted for age and sex) was decreased by only 10%, and the standardized effect size (Cohen´s d) was smaller than that of pTau217. Tau-IP did not improve the performance of the pTau217 assay (p = 0.568, DeLong test). However, the Aβ1-40/Aβ1-42*pTau217 ratio following immunoprecipitations appeared to outperform the single blood biomarkers.</p> Conclusion <p>PTau217 as measured with the fully automated Lumipulse G pTau217 Plasma &lt; RUO &gt; assay demonstrated high accuracy for detecting low CSF Aβ1-42/1-40 and appears to represent a particularly attractive biomarker for future implementation in clinical practice. Furthermore, the composite score Aβ1-40/Aβ1-42*pTau217 showed promise for enhancing the blood-based early and differential diagnosis of AD.</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

Evaluation of a fully automated assay for the measurement of plasma pTau217 and a composite score integrating the ratio Aβ1-42/1-40 as biomarkers of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月27日

查看全文
  • Barbara Morgado,
  • Hans-Wolfgang Klafki,
  • Chris Bauer,
  • Annik Steiert,
  • Katharina Waniek,
  • Ingolf Lachmann,
  • Dirk Osterloh,
  • Hermann Esselmann,
  • Niels Hansen,
  • Johannes Schuchhardt,
  • Jens Wiltfang

摘要

Background

Plasma phosphorylated Tau217 (pTau217) represents a sensitive blood-based biomarker for Alzheimer’s disease (AD). This study investigated the performance of plasma pTau217 alone and as a composite score (Aβ1-40/Aβ1-42*pTau217) for detecting low Aβ1-42/1-40 in cerebrospinal fluid (CSF) as a surrogate marker of brain β-amyloid pathological changes.

Methods

We analysed plasma samples from 82 pre-selected participants who were dichotomized according to their CSF Aβ42/40 ratio after data-driven cutoff determination by Gaussian mixture modelling. The study cohort included patients in very early disease stages with mild cognitive impairment (MCI) due to AD and mild dementia due to AD in the Aβ-positive group and MCI due to other causes and mild dementia due to other causes in the Aβ-negative group. Concentrations of plasma pTau181 and pTau217 were determined on the fully automated LUMIPULSE platform. Additionally, plasma Aβ1-42/1-40 and pTau217 were assessed after consecutive Aβ- and Tau-immunoprecipitations (IPs). Corrections for age and sex effects in primary variables were done using a multivariate linear model on a logarithmic scale. Results are reported using both adjusted and unadjusted values.

Results

After adjustment for age and sex, median plasma pTau217 was increased by 203% in participants with low CSF Aβ1-42/1-40 (i.e. Aβ-positive), while pTau181 was increased by only 61%. PTau217 showed a larger area under the receiver operating characteristics curve (AUC) of 0.88 in identifying Aβ-positive individuals compared to plasma pTau181 (AUC: 0.78). Plasma Aβ1-42/1-40 ratio in Aβ-IP eluates (adjusted for age and sex) was decreased by only 10%, and the standardized effect size (Cohen´s d) was smaller than that of pTau217. Tau-IP did not improve the performance of the pTau217 assay (p = 0.568, DeLong test). However, the Aβ1-40/Aβ1-42*pTau217 ratio following immunoprecipitations appeared to outperform the single blood biomarkers.

Conclusion

PTau217 as measured with the fully automated Lumipulse G pTau217 Plasma < RUO > assay demonstrated high accuracy for detecting low CSF Aβ1-42/1-40 and appears to represent a particularly attractive biomarker for future implementation in clinical practice. Furthermore, the composite score Aβ1-40/Aβ1-42*pTau217 showed promise for enhancing the blood-based early and differential diagnosis of AD.