Sutherland M K, Wong L, Somerville M J, Handley P, Yoong L, Bergeron C, McLachlan D R
Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada.
Neurobiol Aging. 1992 Mar-Apr;13(2):301-12. doi: 10.1016/0197-4580(92)90043-w.
A history of thyroid dysfunction has been cited as a possible risk factor for Alzheimer's disease (AD). Neurologic symptoms displayed by hypothyroid patients resemble, in part, those manifested by Alzheimer patients. To determine if a relationship exists between thyroid hormone receptor message levels and AD, in situ hybridization with tritiated antisense RNA probes for thyroid hormone receptors was used to examine the expression of these genes in Alzheimer and Huntington brain tissue. Message levels for a thyroid hormone receptor highly expressed in brain (c-ERB A alpha) was reduced by 52% in CA1 and 43% in CA2 in Alzheimer hippocampus as compared to Huntington controls. In contrast, message levels for another form of thyroid hormone receptor (c-ERB A beta 1) in Alzheimer hippocampus were not significantly different from Huntington controls. Temporal and cerebellar levels of c-ERB A alpha were elevated by 1.6-fold whereas temporal but not cerebellar levels of c-ERB A beta 1 were elevated 2.0-fold in Alzheimer brain. There was no correlation between thyroid hormone receptor levels and brain weight, autopsy interval, patient age, or the extent of neurofibrillary degeneration. Instead, decreased thyroid hormone receptor mRNA levels in Alzheimer-affected hippocampus were due to an increase in the percentage of neurons expressing lower message levels for these proteins.
甲状腺功能障碍史被认为是阿尔茨海默病（AD）的一个可能风险因素。甲状腺功能减退患者表现出的神经症状部分类似于阿尔茨海默病患者的症状。为了确定甲状腺激素受体信息水平与AD之间是否存在关联，使用针对甲状腺激素受体的氚标记反义RNA探针进行原位杂交，以检查这些基因在阿尔茨海默病和亨廷顿病脑组织中的表达。与亨廷顿病对照组相比，在阿尔茨海默病海马体中，大脑中高表达的一种甲状腺激素受体（c-ERB Aα）的信息水平在CA1区降低了52%，在CA2区降低了43%。相比之下，阿尔茨海默病海马体中另一种形式的甲状腺激素受体（c-ERB Aβ1）的信息水平与亨廷顿病对照组无显著差异。在阿尔茨海默病大脑中，c-ERB Aα在颞叶和小脑的水平升高了1.6倍，而c-ERB Aβ1仅在颞叶水平升高了2.0倍，小脑水平未升高。甲状腺激素受体水平与脑重量、尸检间隔、患者年龄或神经原纤维变性程度之间无相关性。相反，在受阿尔茨海默病影响的海马体中，甲状腺激素受体mRNA水平降低是由于表达这些蛋白质较低信息水平的神经元百分比增加所致。
