Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease

Grazia D'Onofrio, Francesco Panza, Daniele Sancarlo, Michele Lauriola, Mariangela P. Dagostino, Giulia Paroni, Madia Lozupone, Antonio Mangiacotti, Paola Bisceglia, Carolina Gravina, Maria Urbano, Filomena Addante, Francesco Paris, Leandro Cascavilla, Antonio Greco, Davide Seripa

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Background: Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. Methods: We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. Results: Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121-0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195-4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. Conclusions: More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.

Original languageEnglish
Article number4
JournalTranslational Neurodegeneration
Issue number1
Publication statusPublished - Feb 1 2019


  • 5-HTTLPR
  • Alzheimer's disease
  • Delusions
  • Neuropsychiatric inventory
  • Serotonin

ASJC Scopus subject areas

  • Clinical Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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