Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
J Alzheimers Dis. 2011;26(4):755-766. doi: 10.3233/JAD-2011-110002.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters--glutamate, acetylcholine, dopamine, and serotonin--has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1-3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆丧失和痴呆的行为和心理症状。不同神经递质——谷氨酸、乙酰胆碱、多巴胺和 5-羟色胺——的失衡被认为是 AD 行为症状的神经生物学基础。与 AD 中神经递质失衡相关的分子变化尚不清楚。我们假设通过囊泡谷氨酸转运体（VGLUTs）、兴奋性氨基酸转运体（EAATs）、囊泡乙酰胆碱转运体（VAChT）、5-羟色胺再摄取转运体（SERT）或多巴胺再摄取转运体（DAT）改变神经递质的再摄取与 AD 中的神经递质失衡有关。我们通过检查 10 例 AD 患者和 10 例匹配的非 AD 对照患者死后前额叶皮层中这些转运体的蛋白和 mRNA 水平来检验这一假设。与对照组相比，AD 患者的 VGLUTs、EAAT1-3、VAChT 和 SERT 的蛋白和 mRNA 水平显著降低。DAT 和儿茶酚-O-甲基转移酶的表达不变。VGLUTs 和 EAATs 的减少可能导致谷氨酸能再循环的改变，而 SERT 的减少可能会加重 AD 中的抑郁症状。VAChT 表达的减少可能有助于解释 AD 中明显的胆碱能缺陷。改变的神经递质转运体可能有助于 AD 的病理生理学，并且是潜在的治疗靶点。
