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

Abstract

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.