Ge Feifei, Dong Lin, Zhu Donglin, Lin Xingjian, Shi Jingping, Xiao Ming
Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Province, Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, China.
J Alzheimers Dis. 2022;85(2):605-614. doi: 10.3233/JAD-215092.
Accumulating studies have implicated thyroid dysfunction in the pathogenesis of Alzheimer's disease (AD).
This study aimed to explore the association between thyroid hormone (TH) levels and cerebrospinal fluid (CSF) biomarkers for AD continuum among euthyroid subjects.
In all, 93 clinically euthyroid subjects with a cognitive decline were included in this prospective cross-sectional study and were divided into groups with abnormal AD biomarkers (belonging to the "Alzheimer's continuum"; A+ patients) and those with "normal AD biomarkers" or "non-AD pathological changes" (A-patients), according to the ATN research framework classification for AD. A partial correlation analysis of serum thyroid-stimulating hormone (TSH) or TH levels with CSF biomarkers was conducted. The predictor for A+ patients was analyzed via binary logistic regressions. Finally, the diagnostic significance of individual biochemical predictors for A+ patients was estimated via receiver operating characteristic curve analysis.
Serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels were found to affect the levels of CSF amyloid-β (Aβ)42 and the ratios of Aβ42/40. Further, FT3 was found to be a significant predictor for A+ via binary logistic regression modeling. Moreover, FT3 showed a high diagnostic value for A+ in euthyroid subjects.
Even in a clinical euthyroid state, low serum FT3 and TT3 levels appear to be differentially associated with AD-specific CSF changes. These data indicate that serum FT3 is a strong candidate for differential diagnosis between AD continuum and non-AD dementia, which benefits the early diagnosis and effective management of preclinical and clinical AD patients.
越来越多的研究表明甲状腺功能障碍与阿尔茨海默病（AD）的发病机制有关。
本研究旨在探讨甲状腺激素（TH）水平与甲状腺功能正常的受试者中AD连续体的脑脊液（CSF）生物标志物之间的关联。
在这项前瞻性横断面研究中，共纳入了93名临床甲状腺功能正常但有认知功能下降的受试者，并根据AD的ATN研究框架分类，将其分为AD生物标志物异常组（属于“阿尔茨海默病连续体”；A+患者）和“AD生物标志物正常”或“非AD病理变化”组（A-患者）。对血清促甲状腺激素（TSH）或TH水平与CSF生物标志物进行偏相关分析。通过二元逻辑回归分析A+患者的预测因素。最后，通过受试者工作特征曲线分析评估个体生化预测指标对A+患者的诊断意义。
发现血清总三碘甲状腺原氨酸（TT3）和游离三碘甲状腺原氨酸（FT3）水平会影响CSF淀粉样蛋白-β（Aβ）42水平以及Aβ42/40比值。此外，通过二元逻辑回归建模发现FT3是A+的显著预测指标。而且，FT3对甲状腺功能正常的受试者中的A+具有较高的诊断价值。
即使处于临床甲状腺功能正常状态，血清FT3和TT3水平降低似乎也与AD特异性CSF变化存在差异关联。这些数据表明，血清FT3是AD连续体与非AD痴呆鉴别诊断的有力候选指标，这有利于临床前期和临床AD患者的早期诊断和有效管理。
