Primate-specific genes and isoforms could provide insight into human brain 
diseases. Our bioinformatic analysis revealed that there are possibly five 
isoforms of human GDNF gene with different pre- and pro-regions by inter- and 
intra-exon splicing. By using TaqMan primer probe sets, designed between exons, 
we verified the expression of all isoforms. Furthermore, a novel GDNFOS gene was 
found to be transcribed from the opposite strand of GDNF gene. GDNFOS gene has 
four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are 
long noncoding RNAs, and GDNFOS3 encodes a protein of 105 amino acids. To study 
human GDNF and GDNFOS regulation in neurodegenerative diseases, the protein and 
mRNA levels were measured by Western blot and RT-quantitative PCR, respectively, 
in postmortem middle temporal gyrus (MTG) of Alzheimer disease (AD) and 
Huntington disease (HD) patients in comparison with those of normal controls. In 
the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the 
transcript of GDNF isoform from human exon 2 was up-regulated, whereas that of 
the conserved isoform from exon 1 remained unchanged in comparison with those of 
normal controls. In contrast, the mature GDNF peptide and the isoform mRNA 
levels were not changed in the MTG of HD. The findings of novel GDNF and GDNFOS 
isoforms and differences in tissue expression patterns dysregulated in AD brains 
may further reveal the role of endogenous GDNF in human brain diseases.