Jeong Hyeon Byeon, Min Soo Byun, Dahyun Yi, Joon Hyung Jung, Bo Kyung Sohn, Yoon Young Chang, Nayeong Kong, Gijung Jung, Hyejin Ahn, Jun-Young Lee, Yun-Sang Lee, Yu Kyeong Kim, Dong Young Lee
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Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.</p><p><strong>Methods: </strong>This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [<sup>11</sup>C]-Pittsburgh compound B (PiB)- PET and [<sup>18</sup>F] AV-1451 PET.</p><p><strong>Results: </strong>No associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.</p><p><strong>Conclusion: </strong>Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. 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引用次数: 0
摘要
背景:甲状腺激素水平的改变与阿尔茨海默病(AD)痴呆症和相关认知能力下降的风险增加有关。然而,甲状腺激素与阿尔茨海默病痴呆之间联系的神经病理学基础尚未完全清楚。我们首先研究了血清甲状腺激素水平与体内AD病理学之间的关系,包括通过正电子发射断层扫描(PET)测量的β-淀粉样蛋白(Aβ)和tau沉积。鉴于众所周知的Aβ与AD中tau病理之间的关系,我们还研究了甲状腺激素水平对Aβ与tau沉积之间关系的调节作用:这项横断面研究是韩国阿尔茨海默病早期诊断和预测脑老化研究(KBASE)队列的一部分。这项研究共包括 291 名认知正常的成年人,年龄在 55 至 90 岁之间。所有参与者都接受了全面的临床评估、血清总三碘甲状腺原氨酸(T3)、游离三碘甲状腺原氨酸(fT3)、游离甲状腺素(fT4)和促甲状腺激素(TSH)测量,以及脑成像评估,包括[11C]-匹兹堡化合物 B (PiB)PET 和 [18F] AV-1451 PET:结果:甲状腺激素或促甲状腺激素与 PET 上的 Aβ 和 tau 沉积均无关联。然而,fT4(p = 0.002)和fT3(p = 0.001)与Aβ在tau沉积上有显著的交互作用:剔除一个离群值后进行的敏感性分析表明,fT4 与 Aβ 沉积之间的交互作用不显著,而 fT3 与 Aβ 沉积之间的交互作用仍然显著。然而,进一步的亚组分析表明,无论是否去除离群值,fT4和fT3较高的组别与较低的组别相比,Aβ和tau之间的正相关关系更为明显。同时,T3和TSH与Aβ对tau沉积都没有相互作用:我们的研究结果表明,血清甲状腺激素可能会缓和脑Aβ与tau病理学之间的关系。结论:我们的研究结果表明,血清甲状腺激素可能会缓和脑Aβ与tau病理学之间的关系,较高水平的血清甲状腺激素可能会加速脑Aβ依赖性tau沉积。要验证目前的结果,还需要在独立样本中进行进一步的重复研究。
Moderation of thyroid hormones for the relationship between amyloid and tau pathology.
Background: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.
Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET.
Results: No associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.
Conclusion: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
期刊介绍:
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.