Hazan Jemma, Liu Kathy Y, Zetterberg Henrik, Fox Nick, Howard Robert
Division of Psychiatry, University College London, London, UK.
Dementia Research Institute, University College London, London, UK.
Int J Geriatr Psychiatry. 2025 Aug;40(8):e70138. doi: 10.1002/gps.70138.
Plasma phosphorylated tau (p-tau) levels, such as p-tau181, are elevated in Alzheimer's disease compared to cognitively unimpaired individuals. They represent potential candidate blood biomarkers for use in memory services where CSF examinations are not available. However, the effect of age on plasma p-tau levels remains undetermined. Limited studies have investigated the association between age and plasma p-tau thus far, and fewer still have differentiated levels by brain amyloid pathology. Characterising these associations and determining if this is influenced by sociodemographic factors or medical comorbidities is important for establishing blood biomarker reference ranges.
Using ADNI data, we analysed 860 observations (581 participants; age range: 55-95 years; 56.0% male; 93.6% White). Linear mixed models (LMMs) estimated fixed effects of age, creatinine, baseline BMI, sex, ethnicity, and group (Control vs. AD) on plasma p-tau181 concentration, with a random intercept for participant ID. Separate LMMs assessed covariate effects and interactions with group status.
Analysis of ADNI data revealed a significant positive association between p-tau181 levels, group status, and creatinine in the fully adjusted LLM. Group status may have obscured the total effect of age on p-tau181, as its removal from the model resulted in a significant age effect. Single-variable models showed the positive association between either age, or creatinine and p-tau181 levels did not differ between control and AD groups. There was a significant negative association between BMI and plasma p-tau, which was stronger in AD versus control groups.
This study provides insights into the factors that may influence plasma p-tau181 levels. These findings underscore the need to account for clinical and demographic factors when interpreting p-tau181. Future research should validate these associations in diverse populations and explore underlying mechanisms.
与认知未受损个体相比，阿尔茨海默病患者血浆中磷酸化tau蛋白（p-tau）水平升高，如p-tau181。在无法进行脑脊液检查的记忆服务中，它们是潜在的血液生物标志物候选指标。然而，年龄对血浆p-tau水平的影响仍未确定。迄今为止，仅有有限的研究调查了年龄与血浆p-tau之间的关联，更少的研究按脑淀粉样病变对水平进行区分。明确这些关联并确定其是否受社会人口统计学因素或合并症影响，对于建立血液生物标志物参考范围很重要。
利用阿尔茨海默病神经影像学计划（ADNI）的数据，我们分析了860份观察数据（581名参与者；年龄范围：55 - 95岁；56.0%为男性；93.6%为白人）。线性混合模型（LMMs）估计年龄、肌酐、基线体重指数、性别、种族和组别（对照组与阿尔茨海默病组）对血浆p-tau181浓度的固定效应，并对参与者ID设置随机截距。单独的线性混合模型评估协变量效应以及与组别的交互作用。
对ADNI数据的分析显示，在完全调整的线性混合模型中，p-tau181水平、组别状态和肌酐之间存在显著正相关。组别状态可能掩盖了年龄对p-tau181的总体影响，因为从模型中去除该因素后出现了显著的年龄效应。单变量模型显示，年龄或肌酐与p-tau181水平之间的正相关在对照组和阿尔茨海默病组之间没有差异。体重指数与血浆p-tau之间存在显著负相关，且在阿尔茨海默病组中比对照组更强。
本研究深入探讨了可能影响血浆p-tau181水平的因素。这些发现强调在解释p-tau181时需要考虑临床和人口统计学因素。未来的研究应在不同人群中验证这些关联，并探索潜在机制。
