Role of 5HT (2A) and 5HT (2C) polymorphisms in behavioural and psychological symptoms of Alzheimer's disease

OBJECTIVE: Alzheimer's disease (AD) patients suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. Polymorphisms within serotonin receptors 5HT(2A) and 5HT(2C) have been previously investigated in a few interesting studies reviewed here, however, their role remains unclear. METHODS: Our large cohort of 394 patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period and give each patient a severity score. These measures were related to the 5HT(2A) T102C and 5HT(2C) cys23ser genotype and allele frequencies. RESULTS: Our data supports previous reports of an increased frequency of the C allele and CC genotype of the T102C variant of 5HT(2A) with hallucinations, delusions, psychosis and aberrant motor behaviour, however, we dispute previous associations with depression and aggression. We describe for the first time an increase in the C allele and CC genotype frequencies of the cys23ser variant of 5HT(2C) with anxiety and support previous associations with appetite disturbances in females. CONCLUSION: This review and extension of previous data presents support for the role of 5HT(2A) and 5HT(2C) in the development of certain symptoms, although the effect size may be small.