与轻度认知障碍(MCI)和阿尔茨海默病(AD)的发病和进展相关的外周神经内分泌免疫网络缺陷尚未得到广泛研究。本研究相关地检查了细胞介导的免疫反应之间的关联,压力荷尔蒙,淀粉样前体蛋白(APP)表达,外周血单核细胞(PBMC),与成人相比,MCI和AD病理生理学中的细胞内信号分子。血清APP,淋巴细胞增殖,总胆碱酯酶(TChE),丁酰胆碱酯酶(BChE)活性,细胞因子(IL-2,IFN-γ,IL-6和TNF-α),和胞内信号分子(p-ERK,p-CREB,和p-Akt)在成人的PBMC中测量,老,MCI和AD男性和女性最初和3年后在同一人群中。观察到MCI和AD男性和女性的小型精神状态检查(MMSE)评分和淋巴细胞增殖的年龄和疾病相关下降。与年龄和疾病相关的血清APP增加,皮质醇水平,在男性和女性中观察到TChE活性。增强Th1细胞因子的产生,IL-2,促炎细胞因子,抑制细胞内转录因子可能促进MCI和AD患者的炎症环境。CREB和Akt在MCI和AD男性中表达较低,而p-ERK的表达较高,3年后,MCI和AD女性的p-CREB较低。这些结果表明,特定细胞内信号通路的变化可能会影响细胞介导的免疫力的变化,从而促进MCI和AD患者的疾病进展。
Deficits in the neuroendocrine-immune network in the periphery associated with the onset and progression of mild cognitive impairment (MCI) and Alzheimer\'s disease (AD) have not been extensively studied. The present study correlatively examines the association between cell-mediated immune responses, stress hormones, amyloid precursor protein (APP) expression, peripheral blood mononuclear cells (PBMC), and intracellular signaling molecules in the pathophysiology of MCI and AD compared to adults. Serum APP, lymphocyte proliferation, total cholinesterase (TChE), butyrylcholinesterase (BChE) activities, cytokines (IL-2, IFN-γ, IL-6, and TNF-α), and intracellular signaling molecules (p-ERK, p-CREB, and p-Akt) were measured in the PBMCs of adult, old, MCI, and AD men and women initially and after 3 years in the same population. An age- and disease-associated decline in mini-mental state examination (MMSE) scores and lymphocyte proliferation of MCI and AD men and women were observed. An age- and disease-related increase in serum APP, cortisol levels, and TChE activity were observed in men and women. Enhanced production of Th1 cytokine, IL-2, pro-inflammatory cytokines, and suppressed intracellular transcription factors may promote the inflammatory environment in MCI and AD patients. The expression of CREB and Akt was lower in MCI and AD men, while the expression of p-ERK was higher, and p-CREB was lower in MCI and AD women after 3 years. These results suggest that changes in specific intracellular signaling pathways may influence alterations in cell-mediated immunity to promote disease progression in MCI and AD patients.