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Background <p>While cross-sectional associations between plasma biomarkers and Alzheimer’s disease (AD) pathology and cognition are well established, their longitudinal relationships remain less elucidated. We aimed to explore the utility of plasma β-amyloid (Aβ) 42/Aβ40 and glial fibrillary acidic protein (GFAP) in detecting and predicting AD progression, particularly considering neuroinflammation as a key contributor.</p> Methods <p>Utilizing data from the Sino Longitudinal Study on Cognitive Decline (SILCODE), 455 older Chinese participants with available plasma Aβ42/Aβ40 and GFAP data were enrolled. Based on cohort-derived thresholds of plasma Aβ42/Aβ40 (A) and GFAP (As), participants were divided into four groups: A + As+, A + As-, A-As+, and A-As-. We employed generalized linear models to examine the cross-sectional and longitudinal associations between plasma Aβ42/Aβ40, GFAP, and their combination with plasma phosphorylated tau (p-tau), residual hippocampal volume (rHCV), and cognitive function.</p> Results <p>Among 455 participants (mean [SD] age at baseline, 66.11 [6.73] years; 282 [61.98%] female), the A + As + group consistently demonstrated the highest baseline levels and fastest longitudinal increases in plasma p-tau, alongside the lowest baseline levels and fastest longitudinal deterioration of rHCV and cognition. Lower baseline plasma Aβ42/Aβ40 was associated with worse memory and language cognitive function and higher baseline and accelerated increases in plasma p-tau181 and p-tau217. Elevated baseline plasma GFAP was significantly associated with higher baseline plasma p-tau181 and p-tau217, reduced rHCV and cognition, and predicted more rapid increases in plasma p-tau181 and p-tau217, and faster declines in rHCV and cognition. Longitudinally, plasma GFAP slope was positively related to the slopes of plasma p-tau181 and p-tau217 and rapid decreases in global, memory, and executive cognitive function. In contrast, the plasma Aβ42/Aβ40 slope showed a negative correlation only with the p-tau181 slope.</p> Conclusions <p>These findings demonstrate the superior predictive utility of plasma GFAP in identifying and predicting plasma p-tau increase, neurodegeneration, and cognitive decline than plasma Aβ42/Aβ40 alone. Critically, the combination of both biomarkers yielded the most optimal results, highlighting their synergistic value for early detection and tracking of AD progression.</p>

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Longitudinal characteristics of plasma biomarkers in Chinese older adults with Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月3日

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  • Ruixian Li,
  • Lin Liu,
  • Jie Yang,
  • Wenhui Chai,
  • Mingkai Zhang,
  • Min Wei,
  • Yongzhe Wei,
  • Xuanqian Wang,
  • Shuyu Zhang,
  • Jinghua Wang,
  • Tengfei Guo,
  • Ying Han

摘要

Background

While cross-sectional associations between plasma biomarkers and Alzheimer’s disease (AD) pathology and cognition are well established, their longitudinal relationships remain less elucidated. We aimed to explore the utility of plasma β-amyloid (Aβ) 42/Aβ40 and glial fibrillary acidic protein (GFAP) in detecting and predicting AD progression, particularly considering neuroinflammation as a key contributor.

Methods

Utilizing data from the Sino Longitudinal Study on Cognitive Decline (SILCODE), 455 older Chinese participants with available plasma Aβ42/Aβ40 and GFAP data were enrolled. Based on cohort-derived thresholds of plasma Aβ42/Aβ40 (A) and GFAP (As), participants were divided into four groups: A + As+, A + As-, A-As+, and A-As-. We employed generalized linear models to examine the cross-sectional and longitudinal associations between plasma Aβ42/Aβ40, GFAP, and their combination with plasma phosphorylated tau (p-tau), residual hippocampal volume (rHCV), and cognitive function.

Results

Among 455 participants (mean [SD] age at baseline, 66.11 [6.73] years; 282 [61.98%] female), the A + As + group consistently demonstrated the highest baseline levels and fastest longitudinal increases in plasma p-tau, alongside the lowest baseline levels and fastest longitudinal deterioration of rHCV and cognition. Lower baseline plasma Aβ42/Aβ40 was associated with worse memory and language cognitive function and higher baseline and accelerated increases in plasma p-tau181 and p-tau217. Elevated baseline plasma GFAP was significantly associated with higher baseline plasma p-tau181 and p-tau217, reduced rHCV and cognition, and predicted more rapid increases in plasma p-tau181 and p-tau217, and faster declines in rHCV and cognition. Longitudinally, plasma GFAP slope was positively related to the slopes of plasma p-tau181 and p-tau217 and rapid decreases in global, memory, and executive cognitive function. In contrast, the plasma Aβ42/Aβ40 slope showed a negative correlation only with the p-tau181 slope.

Conclusions

These findings demonstrate the superior predictive utility of plasma GFAP in identifying and predicting plasma p-tau increase, neurodegeneration, and cognitive decline than plasma Aβ42/Aβ40 alone. Critically, the combination of both biomarkers yielded the most optimal results, highlighting their synergistic value for early detection and tracking of AD progression.