REDUCTION OF THYROID-HORMONE RECEPTOR C-ERB A-ALPHA MESSENGER-RNA LEVELS IN THE HIPPOCAMPUS OF ALZHEIMER AS COMPARED TO HUNTINGTON BRAIN

A history of thyroid dysfunction has been cited as a possible risk fac tor for Alzheimer's disease (AD). Neurologic symptoms displayed by hyp othyroid patients resemble, in part, those manifested by Alzheimer pat ients. To determine if a relationship exists between thyroid hormone r eceptor message levels and AD, in situ hybridization with tritiated an tisense RNA probes for thyroid hormone receptors was used to examine t he expression of these genes in Alzheimer and Huntington brain tissue. Message levels for a thyroid hormone receptor highly expressed in bra in (c-ERB A-alpha) was reduced by 52% in CA 1 and 43% in CA2 in Alzhei mer hippocampus as compared to Huntington controls. In contrast, messa ge levels for another form of thyroid hormone receptor (c-ERB A-beta-1 ) in Alzheimer hippocampus were not significantly different from Hunti ngton controls. Temporal and cerebellar levels of c-ERB A-alpha were e levated by 1.6-fold whereas temporal but not cerebellar levels of c-ER B A-beta-1 were elevated 2.0-fold in Alzheimer brain. There was no cor relation between thyroid hormone receptor levels and brain weight, aut opsy interval, patient age, or the extent of neurofibrillary degenerat ion. Instead, decreased thyroid hormone receptor mRNA levels in Alzhei mer-affected hippocampus were due to an increase in the percentage of neurons expressing lower message levels for these proteins.