Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
Department of Molecular Medicine, Institute Ruder Boskovic, Zagreb, Croatia.
Curr Alzheimer Res. 2021;18(7):585-594. doi: 10.2174/1567205018666210917162843.
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.
The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD.
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.
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.
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.
多巴胺能系统在阿尔茨海默病（AD）中功能受损。单胺氧化酶 B（MAOB）的活性在 AD 期间增加，该酶参与多巴胺的降解。此外，AD 患者的海马体和新皮层的死后组织中 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。我们最近表明，携带 MAOB rs1799836 多态性 A 等位基因的患者脑脊液中淀粉样蛋白 β1-42 水平降低。
本研究比较了 MAOB rs1799836 多态性和 APOE，这是散发性 AD 的唯一确认遗传风险因素。
我们纳入了 253 名参与者，其中 127 名患有 AD，57 名患有轻度认知障碍，11 名是健康对照组，58 名患有其他原发性痴呆症。使用 TaqMan SNP 基因分型检测确定 MAOB 和 APOE 多态性。
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。
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。
