Lee Ellen E, Winston-Gray Charisse, Barlow James W, Rissman Robert A, Jeste Dilip V
Department of Psychiatry, University of California San Diego, San Diego, CA, United States.
Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
Front Psychiatry. 2021 Mar 2;11:532624. doi: 10.3389/fpsyt.2020.532624. eCollection 2020.
Cognitive deficits in people with schizophrenia (PWS) are a major predictor of disability and functioning, yet the underlying pathophysiology remains unclear. A possible role of amyloid and tau biomarkers (hallmarks of Alzheimer's disease) is still speculative in schizophrenia. Exosomes or extracellular vesicles, involved with cell-to-cell communication and waste removal, can be used to assay brain-based proteins from peripheral blood. To our knowledge, this is the first study of exosomal amyloid and tau protein levels in PWS. This cross-sectional study included 60 PWS and 60 age- and sex-comparable non-psychiatric comparison subjects (NCs), age range 26-65 years. Assessments of global cognitive screening, executive functioning, psychopathology, and physical measures were conducted. Exosomes were extracted and precipitated from fasting plasma and identified as neuron-derived exosomes (NDEs) or astrocyte-derived exosomes (ADEs). Human-specific ELISAs were used to assay levels of amyloid-beta 1-42 (Aβ42), amyloid-beta 1-40 (Aβ40), and phosphorylated T181 tau (P-T181-tau). Plasma assays for aging biomarkers (C-reactive protein and F2-isoprostanes) were also performed. ADE-Aβ42 levels were higher in PWS compared to NCs, though the other exosomal markers were similar between the two groups. Higher ADE-P-T181-tau levels were associated with worse executive functioning. Among PWS, higher ADE-P-T181-tau levels were associated with less severe negative symptoms and increased F2-isoprostane levels. Astrocyte-derived Aβ marker levels were sensitive and specific in differentiating between diagnostic groups. Among PWS, Aβ40 levels differed most by exosomal origin. Exosomal markers may provide novel insights into brain-based processes (e.g., aging, oxidative stress) from peripheral blood samples.
精神分裂症患者（PWS）的认知缺陷是残疾和功能状况的主要预测指标，但其潜在的病理生理学仍不清楚。淀粉样蛋白和tau生物标志物（阿尔茨海默病的标志）在精神分裂症中的可能作用仍具有推测性。外泌体或细胞外囊泡参与细胞间通讯和废物清除，可用于检测外周血中基于脑的蛋白质。据我们所知，这是第一项关于PWS中外泌体淀粉样蛋白和tau蛋白水平的研究。这项横断面研究纳入了60名PWS和60名年龄及性别匹配的非精神科对照受试者（NCs），年龄范围为26至65岁。进行了整体认知筛查、执行功能、精神病理学和身体测量评估。从空腹血浆中提取并沉淀外泌体，并将其鉴定为神经元来源的外泌体（NDEs）或星形胶质细胞来源的外泌体（ADEs）。使用人特异性酶联免疫吸附测定法检测淀粉样β蛋白1-42（Aβ42）、淀粉样β蛋白1-40（Aβ40）和磷酸化T181 tau（P-T181-tau）的水平。还进行了衰老生物标志物（C反应蛋白和F2-异前列腺素）的血浆检测。与NCs相比，PWS中的ADE-Aβ42水平更高，尽管两组之间的其他外泌体标志物相似。较高的ADE-P-T181-tau水平与较差的执行功能相关。在PWS中，较高的ADE-P-T181-tau水平与较轻的阴性症状和升高的F2-异前列腺素水平相关。星形胶质细胞来源的Aβ标志物水平在区分诊断组方面具有敏感性和特异性。在PWS中，Aβ40水平因外泌体来源的不同而差异最大。外泌体标志物可能为从外周血样本中了解基于脑的过程（如衰老、氧化应激）提供新的见解。
