Department of Epidemiology and Public Health, Institute of Epidemiology and Health Care, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.
BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Neurol Sci. 2021 Dec;42(12):5093-5100. doi: 10.1007/s10072-021-05191-5. Epub 2021 Mar 26.
Serum transthyretin (TTR) may be an early biomarker for Alzheimer's disease and related disorders (ADRD). We investigated associations of TTR measured at baseline with cognitive decline and incident ADRD and whether TTR trajectories differ between ADRD cases and non-cases, over 22 years before diagnosis. A total of 6024 adults aged 45-69 in 1997-1999 were followed up until 2019. TTR was assessed three times, and 297 cases of dementia were recorded. Higher TTR was associated with higher cognitive function at baseline; however, TTR was unrelated to subsequent change in cognitive function. TTR at baseline did not predict ADRD risk (hazard ratio per SD TTR (4.8 mg/dL) = 0.97; 95% confidence interval: 0.94-1.00). Among those later diagnosed with ADRD, there was a marginally steeper downward TTR trajectory than those free of ADRD over follow-up (P=0.050). Our findings suggest TTR is not neuroprotective. The relative decline in TTR level in the preclinical stage of ADRD is likely to be a consequence of disease processes.
血清转甲状腺素蛋白（TTR）可能是阿尔茨海默病和相关疾病（ADRD）的早期生物标志物。我们研究了基线时测量的 TTR 与认知能力下降和 ADRD 发病的相关性，以及在诊断前 22 年，TTR 轨迹是否在 ADRD 病例和非病例之间存在差异。共有 1997-1999 年 45-69 岁的 6024 名成年人接受了随访，直至 2019 年。TTR 评估了三次，记录了 297 例痴呆病例。较高的 TTR 与基线时较高的认知功能相关；然而，TTR 与随后认知功能的变化无关。基线 TTR 不能预测 ADRD 风险（每 SD TTR（4.8 毫克/分升）的风险比=0.97；95%置信区间：0.94-1.00）。在随后被诊断为 ADRD 的患者中，与无 ADRD 的患者相比，在随访期间 TTR 的下降轨迹略陡峭（P=0.050）。我们的研究结果表明 TTR 没有神经保护作用。在 ADRD 的临床前阶段，TTR 水平的相对下降可能是疾病过程的结果。
