Aging and endocrine transition states can significantly impact inflammation across organ systems. Neuroinflammation is well documented in Alzheimer disease (AD). Herein, we investigated neuroinflammation that emerges during mid-life aging, chronological and endocrinological, in the female brain as an early initiating mechanism driving AD risk later in life. Analyses were conducted in a translational rodent model of mid-life chronological and endocrinological aging followed by validation in transcriptomic profiles from women versus age-matched men. In the translational model, the neuroinflammatory profile of mid-life aging in females was endocrine and chronological state specific, dynamic, anatomically distributed, and persistent. Microarray dataset analyses of aging human hippocampus indicated a sex difference in neuroinflammatory profile in which women exhibited a profile comparable to the pattern discovered in our translational rodent model, whereas age-matched men exhibited a profile consistent with low neuroimmune activation. Translationally, these findings have implications for therapeutic interventions during mid-life to decrease late-onset AD risk.

衰老和内分泌过渡状态会严重影响整个器官系统的炎症。神经炎在阿尔茨海默氏病（AD）中有充分文献记载。在本文中，我们调查了在女性大脑的中年衰老期间（按时间顺序和内分泌）出现的神经炎症，这是驱动生命后期AD风险的早期启动机制。在中年时间和内分泌老化的翻译啮齿动物模型中进行了分析，然后对女性与年龄相匹配的男性的转录组谱进行了验证。在转化模型中，女性中年衰老的神经炎症特征是内分泌和按时间顺序排列的特定状态，动态的，解剖上分布的和持久的。人类海马衰老的微阵列数据集分析表明，神经发炎的性别存在差异，其中女性的表现与我们的翻译啮齿动物模型中发现的模式相当，而与年龄匹配的男性表现出的神经免疫激活低。从翻译上说，这些发现对中年期间降低晚期AD风险的治疗干预具有重要意义。