Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Department of Biomedical Engineering, Lund University, Lund, Sweden.
Sci Rep. 2024 Oct 25;14(1):25419. doi: 10.1038/s41598-024-75406-0.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by brain aggregation of β-amyloid (Aβ) peptides and phosphorylated tau (P-tau) proteins. Extracellular vesicles (EVs) can be isolated and studied for potential roles in disease. While several studies have tested plasma-derived EVs in AD, few have analyzed EVs from cerebrospinal fluid (CSF), which are potentially more closely related to brain changes. This study included 20 AD patients and 20 cognitively unimpaired (CU) participants. Using a novel EV isolation method based on acoustic trapping, we isolated and purified EVs from minimal CSF volumes. EVs were lysed and analyzed by immunoassays for P-tau217 and P-tau181. Isolation was confirmed through transmission electron microscopy and the presence of EV-specific markers (CD9, CD63, CD81, ATP1A3). Nanoparticle tracking analysis revealed a high variance in EV distribution. AD patients exhibited increased P-tau181 and decreased P-tau217 in EVs, leading to a higher EV P-tau181/P-tau217 ratio compared to CU. No significant differences in EV counts or sizes were observed between AD and CU groups. This study is the first to use acoustic trapping to isolate EVs from CSF and demonstrates differential P-tau content in AD-derived EVs, warranting further research to understand the relationship between these EV changes and brain pathology.
阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，其特征是大脑中β-淀粉样蛋白（Aβ）肽和磷酸化 tau（P-tau）蛋白的聚集。可以分离和研究细胞外囊泡（EV）在疾病中的潜在作用。虽然已经有几项研究测试了 AD 患者的血浆衍生 EV，但很少有研究分析脑脊液（CSF）中的 EV，因为 CSF 中的 EV 可能与大脑变化更密切相关。本研究纳入了 20 名 AD 患者和 20 名认知正常（CU）参与者。使用基于声捕获的新型 EV 分离方法，我们从最小量的 CSF 中分离和纯化了 EV。通过免疫测定法对 P-tau217 和 P-tau181 对 EV 进行裂解和分析。通过透射电子显微镜和 EV 特异性标志物（CD9、CD63、CD81、ATP1A3）的存在确认了分离。纳米颗粒跟踪分析显示 EV 分布存在高变异性。AD 患者 EV 中的 P-tau181 增加，P-tau217 减少，导致 EV P-tau181/P-tau217 比值高于 CU。AD 和 CU 组之间 EV 计数或大小没有明显差异。本研究首次使用声捕获从 CSF 中分离 EV，并证明 AD 衍生 EV 中 P-tau 含量存在差异，需要进一步研究以了解这些 EV 变化与脑病理学之间的关系。
