REGULATION OF METALLOTHIONEIN-III (GIF) MESSENGER-RNA IN THE BRAIN OFPATIENTS WITH ALZHEIMER-DISEASE IS NOT IMPAIRED

Contradictory results have been reported on the downregulation and rol e of the brain-specific protein metallothionein-III (MT-III, GIF) in A lzheimer disease (AD). Ln this article, the importance of MT-m downreg ulation in AD brain was re-evaluated in temporal and frontal cortex, h ippocampus, and cerebellum of 11 AD patients and two groups of five an d six control subjects, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the levels of MT-III mRN A relative to the levels of three constitutive RNAs: beta-actin, glyce raldehyde-3-phosphate dehydrogenase (G3PDH), and ribosomal RNA 18S (rR NA 18S). The distribution of MT-III was similar to that of each of the three constitutive RNAs. The relative levels of each of these RNAs wa s high in brain regions examined in both AD patients and control subje cts. Our findings do not support a downregulation of MT-III mRNA in th e frontal cortex as well as the temporal cortex and hippocampus of AD patients. However, the level of MT-III mRNA was not constant in the in vestigated samples, suggesting that MT-III mRNA regulation could be co ntrolled by factors other than AD pathology. Brain-derived neurotrophi c factor (BDNF) mRNA levels were hardly detectable by RT-PCR in human brain tissue; a trend for a decrease was apparent in the temporal cort ex of AD patients. In conclusion, the content of MT-III mRNA in the br ain of AD patients was not detectably impaired, whereas BDNF mRNA may be affected.