The Serotonin Transporter Promoter Polymorphic Region is not a Risk Factor for Alzheimer's Disease Related Behavioral Disturbances

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and often accompanied during its progression by behavioral and psychological symptoms of dementia (BPSD). We decided to evaluate the association between AD-related behavioral disturbances and the short/long (S/L) polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). This functional polymorphism modulates SLC6A4 transcription rate, with the S-allele having a 2-fold reduced efficiency, leading to a diminished availability of 5-HT that might in turn trigger behavioral and cognitive alterations. The SLC6A4 promoter functional single nucleotide polymorphism rs25531 (A. G) was genotyped as well. We collected 235 sporadic AD subjects that were classified as AD with (n = 122) or without (n = 113) behavioral alterations, assessed with the Spontaneous Behavior Interview scale, section Behavioral Problems (SBI-BP). Comparing the genotypic and allelic frequencies of AD without and with BPSD, we did not find a difference for the 5-HTTLPR or the rs25531, even after stratification according to single SBI-BP item. We conclude that 5-HTTLPR and rs25531 are not major genetic modulators of BPSD development in AD.