Reduction of thyroid hormone receptor c-ERB A alpha mRNA levels in the hippocampus of Alzheimer as compared to Huntington brain.

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.