Affiliations: [a] Department of Neuroscience, “Mario Negri” Institute for Pharmacological Research, Milan, Italy | [b] Neurology Unit, Luigi Sacco Hospital, University of Milan, Milan, Italy | [c] Geriatric Division, Ospedali Regionali of Lugano and Mendrisio, Switzerland | [d] Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, “Fondazione Ospedale Maggiore Policlinico”, Milan, Italy
Correspondence:
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Corresponding author: Dr. Diego Albani, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156 Milan, Italy. Tel.: +39 02 39014594; Fax: +39 02 3546277; E-mail: [email protected].
Note: [] Communicated by Alessandro Serretti
Abstract: 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.
Keywords: Alzheimer's disease, behavioral and psychological symptoms of dementia (BPSD), genetics, 5-HTTLPR, rs25531, serotonin, serotonin transporter
