5-HT2A AND 5-HT2C RECEPTOR POLYMORPHISMS AND PSYCHOPATHOLOGY IN LATE-ONSET ALZHEIMERS-DISEASE

The psychopathology of Alzheimer's disease (AD) is varied and includes both behavioural and psychological symptoms. Behavioural and psycholo gical symptoms are common and contribute to the difficulties experienc ed by carers, However, the mechanism whereby these symptoms occur in s ome individuals with AD is not understood. We hypothesized that common genetic polymorphisms in neurotransmitter systems are risk factors fo r these symptoms in the course of AD. A total of 211 subjects from a p opulation-based prospective study of psychopathology within late-onset AD were genotyped for the 5-HT2A receptor polymorphism 102-T/C and th e 5-HT2C receptor polymorphism Cys23Ser, Associations were found betwe en the presence of the C102 allele and the presence of visual (Fisher' s exact test, one-tailed, P = 0.003) and auditory hallucinations (Fish er's exact test, one-tailed, P = 0.004) and between the presence of th e Ser23 allele and visual hallucinations (chi(2) = 7.5, df = 1, P = 0. 006) (P = 0.03, 0.04 and 0.06, respectively, after Bonferroni correcti on), In addition, there was an association between the Cys23Ser polymo rphism and hyperphagia (chi(2) = 6.7, df = 2, P = 0.03) (P = 0.3 after Bonferroni correction). We conclude that common 5-HT2A and 5-HT2C gen etic polymorphisms previously showing only weak associations with psyc hotic illness are associated with psychotic symptoms in AD but are cli nically silent until the onset of the neurodegenerative process.