A new brain-derived neurotrophic factor transcript and decrease inbrain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex
Article first published online: 3 FEB 2004
Journal of Neurochemistry
Volume 82, Issue 5, pages 1058–1064, September 2002
How to Cite
Garzon, D., Yu, G. and Fahnestock, M. (2002), A new brain-derived neurotrophic factor transcript and decrease inbrain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex. Journal of Neurochemistry, 82: 1058–1064. doi: 10.1046/j.1471-4159.2002.01030.x
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Received February 20, 2002; revised manuscript received May 10, 2002; accepted May 13, 2002.
- brain-derived neurotrophic factor;
- gene expression;
Brain-derived neurotrophic factor (BDNF) supports hippocampal, cortical and basal forebrain cholinergic neurons, which lose function in Alzheimer's disease. In Alzheimer's tissues such as hippocampus and parietal cortex, brain- derived neurotrophic factor mRNA is decreased three- to four-fold compared with controls. However, the molecular mechanism of the down-regulation of BDNF in Alzheimer's disease is unknown. The human brain-derived neurotrophic factor gene has multiple promoters governing six non-coding upstream exons that are spliced to one downstream coding exon, leading to six different transcripts. Here we report an alternate human splice variant within exon 4I for a total of seven transcripts. Previous brain-derived neurotrophic factor mRNA measurements in Alzheimer's disease tissue were done using the downstream coding exon present in all transcripts. Using RT-PCR primers specific for each upstream exon, we observe a significant decrease in three human brain-derived neurotrophic factor mRNA transcripts in Alzheimer's disease samples compared with controls. Transcripts 1 and 3 each exhibit a two-fold decrease, and transcript 2 shows a five-fold decrease. There are no significant differences between control and Alzheimer's disease samples for the other transcripts, including the new splice variant. In rat, both transcripts 1 and 3 are regulated through the transcription factor cAMP response element binding protein, whose phosphorylation is decreased in the Alzheimer's disease brain. This could lead to specific down-regulation of the brain-derivedneurotrophic factor transcripts shown here.