Increasing evidence suggests that extracellular vesicles (EVs) – nano-sized particles released from nearly all cell types – contribute to the pathophysiology of several neurodegenerative disorders, including Alzheimer’s disease (AD). To date, brain-EVs have been isolated from postmortem brain tissues, and new approaches are needed to isolate EVs from the brain of live animals. A study by Pait et al. reports a novel method for collecting EVs from the hippocampal interstitial fluid (EV^ISF) of unanesthetized, freely moving mice using in vivo microdialysis. The investigators collected EV^ISF from 3- and 9-month-old male and female APP/PS1 mice – a mouse model of AD – or littermate controls, and analyzed their size, concentration and proteome. The results reveal EV^ISF changes with AD pathogenesis, including a decrease in protein diversity and sex-specific changes in microglia-related EV proteins that correlate with AD-related pathology.

越来越多的证据表明，细胞外囊泡（EV）——几乎所有细胞类型释放的纳米级颗粒——有助于多种神经退行性疾病的病理生理学，包括阿尔茨海默病（AD）。迄今为止，脑电动汽车已从死后脑组织中分离出来，并且需要新的方法从活体动物的大脑中分离电动汽车。派特等人的一项研究。报道了一种使用体内微透析从未麻醉、自由活动的小鼠的海马间质液（EV ^ISF ）中收集 EV 的新方法。研究人员从 3 个月和 9 个月大的雄性和雌性 APP/PS1 小鼠（AD 小鼠模型）或同窝对照小鼠中收集了 EV ^ISF ，并分析了它们的大小、浓度和蛋白质组。结果揭示了 EV ^ISF随 AD 发病机制的变化，包括蛋白质多样性的减少以及与 AD 相关病理相关的小胶质细胞相关 EV 蛋白的性别特异性变化。