【摘要】 目的：探讨阿尔茨海默病（AD）患者脑脊液（CSF）中衔接蛋白复合物2（AP2）的水平与AD病理、脑结构变化及认知功能的关联。方法：本研究纳入了来自AD神经影像学倡议数据库的138例AD患者、403例轻度认知障碍患者（MCI）和167名认知功能正常者（CN），测量其CSF中AP2（α2和β1亚基）水平；收集基线及五年随访期间的AD核心生物标志物浓度，数据包括β-淀粉样蛋白1-42(Aβ₄₂)、总tau蛋白（t-Tau）和磷酸化tau蛋白（p-Tau181）；脑结构数据包括脑室体积、海马体积和内嗅皮层厚度；认知功能评分数据包括简易智力状态检查量表（MMSE）、临床痴呆评分总和量表（CDRSB）。采用单因素协方差分析、多元线性回归模型和线性混合效应模型进行统计分析。结果：在基线时，CSF中AP2水平在CN组、MCI组和AD组间无显著差异，但在载脂蛋白（APOE）ε4携带者中均显著升高。随着年龄的增长，CSF中AP2水平呈上升趋势，与AD病理进展一致。CSF中AP2水平升高与CSF Aβ₄₂、t-Tau、p-Tau181浓度升高以及脑室体积更小呈显著相关，尤其在CN、MCI阶段更为显著。CSF AP2β1与CDRSB呈负相关，与海马体积和内嗅皮层厚度呈正相关。此外，CSF中AP2影响纵向脑结构及认知的改变，尤其在非AD组中更为显著。结论：CSF中AP2可能参与早期Aβ和Tau病理，并与脑室体积、海马体积、内嗅皮层厚度和认知的改变密切相关，尤其在AD的前临床和前驱阶段。更多还原

【Abstract】 Objective: To explore the association between the levels of adaptor protein complex 2（AP2） in cerebrospinal fluid（CSF） of patients with Alzheimer’s disease（AD） and AD pathology, brain structural changes, and cognitive function. Methods: This study enrolled 138 patients with Alzheimer’s disease（AD）, 403 patients with mild cognitive impairment（MCI）, and 167 cognitively normal（CN） subjects from the Alzheimer’s Disease Neuroimaging Initiative（ADNI） database. Levels of AP2（α2 and β1 subunits） in the cerebrospinal fluid（CSF） were measured. Data on core AD biomarkers, including amyloid-beta 1-42(Aβ₄₂), total tau protein（t-Tau）, and phosphorylated tau at threonine 181(p-Tau₁₈₁), brain structural measures including ventricular volume, hippocampal volume, and entorhinal cortex thickness, and cognitive scores, including the Mini-Mental State Examination（MMSE） and the Clinical Dementia Rating-Sum of Boxes（CDRSB） were collected at baseline and over a five-year follow-up period. Statistical analyses were performed using one-way analysis of covariance, multiple linear regression models, and linear mixed-effects models. Results: At baseline, there were no significant differences in CSF AP2 levels among the CN, MCI, and AD groups, but they were significantly elevated in apolipoprotein（APOE） ε4 carriers. CSF AP2 levels increased with age, consistent with AD pathology progression. Elevated CSF AP2 levels were significantly associated with increased CSF Aβ42, T-tau, and p-Tau181 concentrations and smaller ventricular volume, especially in the CN and MCI stages. CSF AP2β1 was negatively correlated with CDRSB and positively correlated with hippocampal volume and entorhinal cortex thickness. Additionally, CSF AP2 affected longitudinal changes in brain structure and cognition, particularly in the non-AD group. Conclusion: CSF AP2 may be involved in early Aβ and tau pathology and is closely related to changes in ventricular volume, hippocampal volume, entorhinal cortex thickness, and cognition, especially in the preclinical and prodromal stages of AD.更多还原