No association between tryptophan hydroxylase gene polymorphism and Alzheimer's disease

Serotonergic dysfunction is implicated in Alzheimer's disease (AD) on the basis of studies of serotonin and its metabolite in postmortem specimens and CSF. There were also reports on association of a tryptophan hydroxylase (TPH) intron 7 variant and CSF 5-hydroxyindoleacetic acid concentrations. These suggested TPH might be a candidate to study for possible involvement in AD. Using a case-control association approach, we studied the TPH polymorphism in 150 subjects with AD and 100 controls. There were no significant differences in genotype or allele frequencies between controls and AD patients. The negative findings suggested that this TPH polymorphism has no major effect on the development of AD. However, the genetic variation of the TPH gene related to the symptomatology of AD deserves further investigation.