Background: The dopaminergic system is functionally compromised in Alzheimer’s Disease (AD). The activity of Monoamine Oxidase B (MAOB), the enzyme involved in the degradation of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the postmortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism modulates MAOB transcription, consequently influencing protein translation and MAOB activity. We recently showed that cerebrospinal fluid levels of amyloid β1-42 are decreased in patients carrying the A allele in MAOB rs1799836 polymorphism.

Objective: The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD.

Methods: We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment, 11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and APOE polymorphisms were determined using TaqMan SNP Genotyping Assays.

Results: We observed that the frequency of APOE ε4/ε4 homozygotes and APOE ε4 carriers is significantly increased among patients carrying the AA MAOB rs1799836 genotype.

Conclusion: These results indicate that the MAOB rs1799836 polymorphism is a potential genetic biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission and cognitive deterioration in AD.

背景：阿尔茨海默病 (AD) 中的多巴胺能系统功能受损。单胺氧化酶 B (MAOB) 是一种参与多巴胺降解的酶，其活性在 AD 期间增加。此外，AD 患者死后海马和新皮质中 MAOB 的表达增加。MAOB rs1799836 多态性调节 MAOB 转录，从而影响蛋白质翻译和 MAOB 活性。我们最近发现携带 MAOB rs1799836 多态性中的 A 等位基因的患者脑脊液中淀粉样蛋白 β1-42 的水平降低。

目的：本研究比较 MAOB rs1799836 多态性和 APOE，这是唯一确认的散发性 AD 遗传风险因素。

方法：我们纳入了 253 名参与者，其中 127 人患有 AD，57 人患有轻度认知障碍，11 人是健康对照组，58 人患有其他原发性痴呆症。MAOB 和 APOE 多态性使用 TaqMan SNP 基因分型测定法确定。

结果：我们观察到携带 AA MAOB rs1799836 基因型的患者中 APOE ε4/ε4 纯合子和 APOE ε4 携带者的频率显着增加。

结论：这些结果表明，MAOB rs1799836 多态性是 AD 的潜在遗传生物标志物，也是治疗 AD 中多巴胺能传递减少和认知恶化的潜在靶点。