Behrens Anders, Anderberg Peter, Berglund Johan Sanmartin, Cianchetta-Sivoriceruti Malena, Dallora Ana Luiza
Department of Health Blekinge Institute of Technology Karlskrona Sweden.
Department of Medicine Blekinge Hospital Karlskrona Sweden.
Alzheimers Dement (Amst). 2025 Sep 8;17(3):e70181. doi: 10.1002/dad2.70181. eCollection 2025 Jul-Sep.
Blood-based biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accessibility, but their clinical interpretation requires understanding of variability and biological influences.
We repeatedly sampled blood from 57 adults referred for lumbar puncture as part of a cognitive evaluation at a memory clinic. We measured serum phosphorylated- tau-181 (s-p-tau181) and plasma amyloid beta (Aβ)42/40 ratio (p-Aβ42/Aβ40) and evaluated the impact of renal and blood-brain barrier (BBB) function.
Test-retest analysis revealed large variability of s-p-tau181 and small for p-Aβ42/Aβ40. Markers of renal function and BBB integrity significantly influenced s-p-tau181 levels, whereas p-Aβ42/Aβ40 was not affected.
This study emphasizes the need for caution when interpreting longitudinal changes in s-p-tau181. Inter-individual variability is to a large degree due to susceptibility to biological influences where a novel association with integrity of BBB function were identified. These results have implications for the clinical application of blood-based biomarkers in AD diagnostics and monitoring.
Blood phosphorylated- tau-181 (p-tau181) shows high test-retest variability in memory clinic patients.Blood amyloid beta (Aβ)42/Aβ40 ratio is stable but has poor diagnostic accuracy.Renal function and blood-brain barrier (BBB) integrity affect blood p-tau181 levels.Caution is needed when interpreting longitudinal changes in blood p-tau181.Renal and BBB disorders should be considered when assessing blood p-tau181.
用于阿尔茨海默病（AD）的血液生物标志物有潜力提高诊断的可及性，但其临床解读需要了解变异性和生物学影响。
我们对57名因认知评估而在记忆门诊接受腰椎穿刺的成年人进行了多次血液采样。我们测量了血清磷酸化tau-181（s-p-tau181）和血浆淀粉样蛋白β（Aβ）42/40比值（p-Aβ42/Aβ40），并评估了肾功能和血脑屏障（BBB）功能的影响。
重测分析显示s-p-tau181的变异性大，而p-Aβ42/Aβ40的变异性小。肾功能和BBB完整性标志物显著影响s-p-tau181水平，而p-Aβ42/Aβ40不受影响。
本研究强调在解释s-p-tau181的纵向变化时需要谨慎。个体间变异性在很大程度上归因于对生物学影响的易感性，其中发现了与BBB功能完整性的新关联。这些结果对基于血液的生物标志物在AD诊断和监测中的临床应用具有启示意义。
血液磷酸化tau-181（p-tau181）在记忆门诊患者中显示出高重测变异性。血液淀粉样蛋白β（Aβ）42/Aβ40比值稳定但诊断准确性差。肾功能和血脑屏障（BBB）完整性影响血液p-tau181水平。在解释血液p-tau181的纵向变化时需要谨慎。在评估血液p-tau181时应考虑肾脏和BBB疾病。
