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阿尔茨海默病患者死后大脑前额叶皮质中的甲状腺激素水平。

Thyroid hormone levels in the prefrontal cortex of post-mortem brains of Alzheimer's disease patients.

作者信息

Davis Jennifer Duncan, Podolanczuk Anna, Donahue John E, Stopa Edward, Hennessey James V, Luo Lu-Guong, Lim Yow-Pin, Stern Robert A

机构信息

Warren Alpert Medical School of Brown University, Department of Psychiatry, Rhode Island Hospital, Providence, RI 02903, USA.

出版信息

Curr Aging Sci. 2008 Dec;1(3):175-81. doi: 10.2174/1874609810801030175.

Abstract

Converging evidence suggests a possible link between thyroid state and Alzheimer's disease (AD), including a higher probability of dementia in individuals with higher TSH levels and a two-fold risk of AD in patients with hypothyroidism. Thyroid hormones modulate factors associated with AD, including amyloid precursor protein expression in the brain, suggesting a possible role for thyroid hormone in AD pathology. The present study is the first to directly evaluate brain thyroid hormone levels in AD. Triiodothyronine (T(3)) and thyroxine (T(4)) levels were measured with radioimmunoassay (RIA) in post-mortem samples of prefrontal cortex of patients with pathologically confirmed AD, including Braak stage I-II (n=8), Braak stage V-VI (n=8), and controls without any primary neurological disease (n=8). T(4) levels did not differ between groups. T(3) levels were significantly lower in Braak stage V-VI brains relative to controls, but there was no statistically significant difference between T(3) levels in Braak stage I-II versus controls. Results suggest that the conversion of T(4) to T(3) may be affected in advanced AD, perhaps due to alterations in deiodinase activity. Reduced conversion of T(4) to T(3) in AD may be associated with both AD pathology and the clinical presentation of dementia.

摘要

越来越多的证据表明甲状腺状态与阿尔茨海默病(AD)之间可能存在联系,包括促甲状腺激素(TSH)水平较高的个体患痴呆症的可能性更高,以及甲状腺功能减退患者患AD的风险增加两倍。甲状腺激素可调节与AD相关的因素,包括大脑中淀粉样前体蛋白的表达,这表明甲状腺激素在AD病理过程中可能发挥作用。本研究首次直接评估AD患者大脑中的甲状腺激素水平。采用放射免疫分析法(RIA)测量了病理确诊为AD的患者前额叶皮质尸检样本中的三碘甲状腺原氨酸(T(3))和甲状腺素(T(4))水平,其中包括Braak I-II期(n = 8)、Braak V-VI期(n = 8)以及无任何原发性神经系统疾病的对照组(n = 8)。各组之间T(4)水平无差异。与对照组相比,Braak V-VI期大脑中的T(3)水平显著降低,但Braak I-II期与对照组之间的T(3)水平无统计学显著差异。结果表明,在晚期AD中,T(4)向T(3)的转化可能受到影响,这可能是由于脱碘酶活性的改变所致。AD中T(4)向T(3)转化的减少可能与AD病理以及痴呆的临床表现均有关。

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