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. 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. 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. 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.

中文翻译：

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羟色胺转运蛋白基因连锁多态性区域（5HTTLPR）与阿尔茨海默病的妄想有关


阿尔茨海默病（AD）妄想症状背后的血清素能途径尚未完全阐明。 5-羟色胺转运蛋白基因连锁多态性区域（5-HTTLPR）是影响转录的血清素转运蛋白编码基因启动子区域中可变数量的串联重复序列。我们根据美国国家老龄化研究所-阿尔茨海默病协会的标准，对总共 257 名临床诊断为 AD 的连续患者调查了 5-HTTLPR 与妄想的关联。所有参与者都接受了标准化综合老年评估和神经精神病学调查的综合评估。 171名患者（66.54%）出现妄想症状。相对于无妄想的 AD 患者，有妄想的 AD 患者显示 S+ 携带者的患病率较低（5-HTTLPR-L/S + 5-HTTLPR-S/S 基因型）[p < 0.001；p < 0.001；比值比 (OR) = 0.240，95% 置信区间 (CI) = 0.121–0.471]。针对载脂蛋白 E 多态性进行调整的 Logistic 回归分析表明，在患有妄想症的 AD 患者中，5-HTTLPR-S 等位基因的存在可能会缩短疾病持续时间（p = 0.005；OR = 0.680，95% CI = 0.522–0.886）并增加异常妄想症。运动活动（p = 0.013；OR = 2.257，95% CI = 1.195–4.260）。目前的研究结果表明 5-HTTLPR 可能与 AD 妄想有关。 S-plus 携带者可能与 AD 妄想的保护作用有关。需要对更广泛的精选痴呆患者样本进行更多研究来证实我们的结果。 然而，目前的研究结果表明，与血清素代谢相关的遗传因素可能对 AD 中神经精神簇的临床表达发挥保护作用，这对于妄想的潜在机制及其在 AD 和痴呆谱系中的可能治疗具有重要意义。