Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.
J Alzheimers Dis. 2021;81(3):1181-1194. doi: 10.3233/JAD-200619.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. One of the pathologies of AD is the accumulation of amyloid-β (Aβ) to form senile plaques, leading to a decline in cognitive ability and a lack of learning and memory. However, the cause leading to Aβ aggregation is not well understood. Dendritic cell factor 1 (Dcf1) shows a high expression in the entorhinal cortex neurons and neurofibrillary tangles in AD patients.
Our goal is to investigate the effect of Dcf1 on Aβ aggregation and memory deficits in AD development.
The mouse and Drosophila AD model were used to test the expression and aggregation of Aβ, senile plaque formation, and pathological changes in cognitive behavior during dcf1 knockout and expression. We finally explored possible drug target effects through intracerebroventricular delivery of Dcf1 antibodies.
Deletion of Dcf1 resulted in decreased Aβ42 level and deposition, and rescued AMPA Receptor (GluA2) levels in the hippocampus of APP-PS1-AD mice. In Aβ42 AD Drosophila, the expression of Dcf1 in Aβ42 AD flies aggravated the formation and accumulation of senile plaques, significantly reduced its climbing ability and learning-memory. Data analysis from all 20 donors with and without AD patients aged between 80 and 90 indicated a high-level expression of Dcf1 in the temporal neocortex. Dcf1 contributed to Aβ aggregation by UV spectroscopy assay. Intracerebroventricular delivery of Dcf1 antibodies in the hippocampus reduced the area of senile plaques and reversed learning and memory deficits in APP-PS1-AD mice.
Dcf1 causes Aβ-plaque accumulation, inhibiting dcf1 expression could potentially offer therapeutic avenues.
阿尔茨海默病（AD）是一种进行性神经退行性疾病。AD 的病理学之一是淀粉样β（Aβ）的积累形成老年斑，导致认知能力下降和学习记忆缺乏。然而，导致 Aβ聚集的原因尚不清楚。树突细胞因子 1（Dcf1）在 AD 患者的内嗅皮层神经元和神经纤维缠结中表达较高。
我们的目标是研究 Dcf1 对 AD 发展中 Aβ聚集和记忆缺陷的影响。
使用小鼠和果蝇 AD 模型来测试 Aβ的表达和聚集、老年斑形成以及认知行为的病理变化，在 dcf1 敲除和表达期间。最后，我们通过脑室内给予 Dcf1 抗体探索了可能的药物靶点效应。
Dcf1 的缺失导致 APP-PS1-AD 小鼠海马中 Aβ42 水平和沉积减少，并且 AMPA 受体（GluA2）水平得到恢复。在 Aβ42 AD 果蝇中，Dcf1 在 Aβ42 AD 果蝇中的表达加剧了老年斑的形成和积累，显著降低了其攀爬能力和学习记忆。对 20 名年龄在 80 至 90 岁之间的 AD 患者和无 AD 患者的数据分析表明，Dcf1 在颞叶皮质中有高水平表达。UV 光谱测定法表明 Dcf1 有助于 Aβ聚集。脑室内给予 Dcf1 抗体可减少海马中的老年斑面积，并逆转 APP-PS1-AD 小鼠的学习和记忆缺陷。
Dcf1 导致 Aβ 斑块堆积，抑制 dcf1 表达可能提供治疗途径。
