CoEN5025 NANOSYN: Unravelling synaptic pathology in Alzheimer's disease and Dementia with Lewy bodies using super-resolution microscopy

CoEN5025 NANOSYN：使用超分辨率显微镜揭示阿尔茨海默病和路易体痴呆症的突触病理学

• 批准号: MR/V00610X/1
• 负责人: Tara Spires-Jones
• 金额: $ 20.16万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV00610X%2F1
• 关键词: CoEN5025; NANOSYN; Unravelling; synaptic; pathology

Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) are the two most common causes of dementia. In order to find effective treatments, it is critical that we understand the exact causes. Accumulation of Abeta and tau proteins in the brain occurs early in people with AD. In DLB, a protein called alpha-synuclein accumulates early inside neurons. We know that synapses, the most critical structures for communication between neurons, are lost very early in these diseases. However, the precise mechanism by which these proteins damage synapses is poorly understood due to the lack of adequate techniques. Here, we will apply the most advanced tools available to investigate the presence of abnormal proteins at synapses in a unique set of human brain samples. We will also investigate the effects of toxic proteins on synapse composition. This information will be invaluable for the development of more specific treatments for the two most common causes of dementia.

阿尔茨海默病（AD）和路易体痴呆（DLB）是痴呆的两个最常见的原因。为了找到有效的治疗方法，我们必须了解确切的原因。在AD患者中，Abeta和tau蛋白在大脑中的积累发生在早期。在DLB中，一种称为α-突触核蛋白的蛋白质在神经元内早期积累。我们知道，突触是神经元之间最关键的通讯结构，在这些疾病中很早就失去了。然而，由于缺乏足够的技术，这些蛋白质损害突触的确切机制知之甚少。在这里，我们将应用最先进的工具来研究一组独特的人脑样本中突触处异常蛋白的存在。我们也将研究毒性蛋白质对突触组成的影响。这些信息对于开发针对痴呆症两种最常见原因的更具体的治疗方法将是非常宝贵的。

项目成果

Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease

• DOI: 10.1111/ene.15043
• 发表时间: 2021-08-12
• 期刊: EUROPEAN JOURNAL OF NEUROLOGY
• 影响因子: 5.1
• 作者: Kurucu, Hatice;Colom-Cadena, Marti;Spires-Jones, Tara L.
• 通讯作者: Spires-Jones, Tara L.