甲状腺功能正常受试者中甲状腺自身免疫状态与阿尔茨海默病生物标志物的关系

IF 3.1 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-12-15 Epub Date: 2025-10-16 DOI:10.1016/j.jneuroim.2025.578780

Feifei Ge , Bo Song , Xixi Wang , Minjie Tian , Xingjian Lin , Jingping Shi , Xing Ye

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引用次数: 0

摘要

背景：甲状腺功能正常个体中甲状腺自身免疫与阿尔茨海默病（AD）生物标志物之间的联系尚不清楚。我们研究了甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TgAb）对AD病理核心脑脊液（CSF）生物标志物的独立和相互作用。方法：我们分析了114名按抗体状态分层的甲状腺功能正常、淀粉样蛋白阳性受试者的脑脊液生物标志物（Aβ1-42、Aβ1-40、T-tau和P-tau181）。使用多元线性回归和四组交叉分类分析评估相关性，调整年龄和性别。结果：TPOAb阳性与脑脊液a - β1-42/ a - β1-40比值显著降低独立相关（平均±SD: 0.04±0.01 vs 0.05±0.02；校正p=0.022; Cohen’SD = -0.65），提示淀粉样蛋白病变更晚期。重要的是，我们发现了一种新的相互作用调节tau病理：分离的TPOAb或TgAb阳性与p -tau181升高有关，但这种作用在两种抗体均阳性的受试者中显着减弱（相互作用p=0.037）。结论：甲状腺自身免疫与AD神经病变相关，与甲状腺激素状态无关。TPOAb与淀粉样蛋白病理的特异性关联以及tau病理抗体之间复杂的相互作用突出了以前未被认识的机制。这些有待纵向研究验证的发现表明，在甲状腺功能正常的老年人中进行甲状腺抗体筛查可能有助于识别阿尔茨海默病的高危人群，可能有助于早期发现和干预。

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Association of thyroid autoimmune status with Alzheimer’s disease biomarkers in euthyroid subjects

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Association of thyroid autoimmune status with Alzheimer’s disease biomarkers in euthyroid subjects

Background:

The link between thyroid autoimmunity and Alzheimer’s disease (AD) biomarkers in euthyroid individuals is poorly understood. We investigated the independent and interactive effects of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) on core cerebrospinal fluid (CSF) biomarkers of AD pathology.

Methods:

We analyzed CSF biomarkers (A

β

1–42, A

β

1–40, T-tau, and P-tau181) measured using validated ELISA assays (Fujirebio) in 114 euthyroid, amyloid-positive participants stratified by antibody status. Associations were assessed using multiple linear regression and four-group cross-classification analyses, adjusting for age and gender.

Results:

TPOAb positivity was independently associated with a significantly lower CSF A

β

1-42/A

β

1-40 ratio (mean ± SD: 0.04 ± 0.01 vs. 0.05 ± 0.02; adjusted p=0.022; Cohen’s d = −0.65), indicating more advanced amyloid pathology. Importantly, we identified a novel interaction modulating tau pathology: isolated positivity for either TPOAb or TgAb was linked to elevated P-tau181, but this effect was significantly attenuated in subjects positive for both antibodies (interaction p=0.037).

Conclusion:

Thyroid autoimmunity is associated with AD neuropathological changes independent of thyroid hormone status. The specific association of TPOAb with amyloid pathology and the complex interplay between antibodies on tau pathology highlight previously unrecognized mechanisms. These findings, pending validation in longitudinal studies, suggest thyroid antibody screening in elderly euthyroid individuals may aid in identifying those at higher risk for Alzheimer’s pathology, potentially facilitating earlier detection and intervention.

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.