HIV相关神经认知紊乱（HAND）在AIDS患者中发病率高，发病机制尚不明确，缺乏早期诊断标志，严重威胁患者生命安全。文献报道：抗dsDNA抗体交叉反应NMDAR可介导的神经兴奋性毒性。课题组前期发现：HIV感染者抗体库有57%是抗dsDNA抗体，而健康人无此类抗体；该种抗体可识别NMDAR，增强Ca2+内流，抑制CREB和Akt活化，使神经细胞凋亡。我们推测：HIV感染者的抗dsDNA抗体可通过交叉反应NMDAR，调控下游CREB-BDNF和PI3K/Akt信号通路，介导HAND发生。本研究拟分析HAND患者血清NMDAR交叉反应性抗dsDNA抗体水平与疾病进程的相关性，并观察细胞和动物实验中CREB-BDNF及PI3K/Akt通路相关分子表达、细胞生存率和小鼠症状，揭示抗dsDNA抗体交叉反应NMDAR参与HAND发生的机制，为HAND早期诊断寻找新的生物标志物提供理论依据。

HIV-associated neurocognitive disorder (HAND) has a high incidence in AIDS patients. The pathogenesis remains to be revealed, and there is a lack of early diagnostic biomarker, which seriously threatens the life of patients. According to the literature, anti-dsDNA antibody cross-reacting with NMDAR can induce neuronal excitotoxicity. Previously, our team found that 57% of the antibodies cloned from HIV-infected individuals were anti-dsDNA antibodies, while there were no such antibodies in healthy people. The anti-dsDNA antibodies could recognize NMDAR, enhance Ca2+ influx, inhibit the activation of CREB and Akt, and finally induce SH-SY5Y cell apoptosis. According to the literature update and our preliminary data, we hypothesize that the anti-dsDNA antibodies of HIV-infected individuals can regulate the downstream CREB-BDNF and PI3K/Akt signaling pathways by cross-reacting with NMDAR, and mediate the occurrence of HAND. We plan to analyze the correlation between the serum NMDAR cross-reactive anti-dsDNA antibody levels and the disease progression in patients with HAND. Then, we will measure the expression and activation levels of molecules and proteins involved in CREB-BDNF and PI3K/Akt signaling pathways and evaluate the cell survival rate in vitro, and symptoms of neuronal cognitive impairment in vivo. This study is aimed to reveal the molecular mechanism of anti-dsDNA cross-reactive with NMDAR in the pathogenesis of HAND, and provide theoretical basis for the finding of new biomarkers to achieve early diagnosis of HAND.