Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
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DOI：
10.1016/j.dadm.2018.11.002
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发表时间：
2019-12-01
影响因子：
5.3
通讯作者：
Rissman, Robert A.
中科院分区：
文献类型：
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作者：
Winston, Charisse N.;Goetzl, Edward J.;Rissman, Robert A.
阿尔茨海默病 (AD) 中异常的血浆星形胶质细胞源性外泌体 (ADE) 中的补体蛋白 (CP) 水平尚未在轻度认知障碍 (MCI) 中进行评估。 方法 参与者（每组 n = 20）有 3 年内 MCI 转变为痴呆 (MCIC)、MCI 3 年内保持稳定 (MCIS)、阿尔茨海默病或对照组。通过抗人谷氨酰胺天冬氨酸转运蛋白抗体吸收从血浆中分离出的ADEs的CP通过ELISA进行定量。结果MCIC患者中经典途径的C1q和C4b、旁路途径的因子D和片段Bb以及两条途径的C5b、C3b和C5b-C9的ADE水平显着高于MCIS患者。 MCIC 患者中抑制性 CP 衰变加速因子、CD46、CD59 和 1 型补体受体的 ADE 水平显着低于 MCIS 患者。 讨论 ADE CP 是神经毒性神经炎症的组成部分，可能是 MCI 转化为阿尔茨海默病的预测生物标志物。
Introduction Levels of complement proteins (CPs) in plasma astrocyte-derived exosomes (ADEs) that are abnormal in Alzheimer's disease (AD) have not been assessed in mild cognitive impairment (MCI).Methods Participants (n = 20 per group) had either MCI converting to dementia within 3 years (MCIC), MCI remaining stable over 3 years (MCIS), Alzheimer's disease, or were controls. CPs of ADEs isolated from plasmas by anti-human glutamine aspartate transporter antibody absorption were quantified by ELISAs.ResultsADE levels of C1q and C4b of the classical pathway, factor D and fragment Bb of the alternative pathway, and C5b, C3b, and C5b-C9 of both pathways were significantly higher in patients with MCIC than those with MCIS. ADE levels of inhibitory CPs decay-accelerating factor, CD46, CD59, and type 1 complement receptor were significantly lower in patients with MCIC than those with MCIS.Discussion ADE CPs are components of neurotoxic neuroinflammation that may be predictive biomarkers of MCI conversion to Alzheimer's disease.