Apolipoprotein E4 (APOE4) and ageing are the most important known risk factors for late-onset Alzheimer’s disease (AD). In the present study, we determined the alterations of IgG, CD19, and Aβ in various brain regions of uninfected male and female APOE3- and APOE4-TR mice at the age of 3 and 10 months to elucidate impacts of AD risk factors on alterations of brain IgG. Positive staining for IgG was distributed across the brain, including neocortex, entorhinal cortex, hippocampus, thalamus and cerebellum. IgG positive staining was mainly located on microglia, but not astrocytes. Some IgG positive neurons were also observed, but only in mediodorsal thalamic nucleus. Compared with APOE3-TR mice, 10-month-old female APOE4-TR mice had lower IgG level in AD susceptible brain regions such as neocortex, entorhinal cortex and hippocampus, but no significant changes in thalamus and cerebellum, two regions nearly intact in AD. In addition, the expression of CD19, a specific marker for mature B cells, was significantly reduced in the hippocampus of 10-month-old female APOE4-TR mice. Although there were no obvious differences in plasma IgG levels between APOE4- and age matched female APOE3-TR mice, significant decreased B cell amount in blood of 10-month-old female APOE4-TR mice have also been found. Moreover, more obvious positive staining for Aβ was observed in the cortex of 10-month-old female APOE4-TR mice than other groups. Our study demonstrated that AD risk factors were associated with IgG alterations in various brain regions, which might result from the defects of humoral immunity and lead to the impairment of IgG-mediated clearance of Aβ by microglia, therefore facilitated AD progression.

中文翻译：

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老年雌性 APOE4-TR 小鼠脑区免疫球蛋白 G 降低伴随 Aβ 积累

载脂蛋白 E4 (APOE4) 和衰老是迟发性阿尔茨海默病 (AD) 最重要的已知风险因素。在本研究中，我们测定了 3 个月和 10 个月大的未感染雄性和雌性 APOE3-和 APOE4-TR 小鼠的不同脑区 IgG、CD19 和 Aβ 的变化，以阐明 AD 危险因素对变化的影响。脑IgG。IgG 阳性染色分布在整个大脑，包括新皮质、内嗅皮质、海马、丘脑和小脑。IgG阳性染色主要位于小胶质细胞，而不是星形胶质细胞。还观察到一些 IgG 阳性神经元，但仅在丘脑背内侧核。与 APOE3-TR 小鼠相比，10 个月大的雌性 APOE4-TR 小鼠在新皮质、内嗅皮质和海马等 AD 易感脑区的 IgG 水平较低，但丘脑和小脑没有显着变化，这两个区域在 AD 中几乎完好无损。此外，成熟 B 细胞的特异性标志物 CD19 的表达在 10 个月大的雌性 APOE4-TR 小鼠的海马中显着降低。虽然 APOE4 和年龄匹配的雌性 APOE3-TR 小鼠之间的血浆 IgG 水平没有明显差异，但也发现了 10 个月大的雌性 APOE4-TR 小鼠血液中 B 细胞数量显着减少。此外，与其他组相比，在 10 个月大的雌性 APOE4-TR 小鼠的皮质中观察到更明显的 Aβ 阳性染色。我们的研究表明，AD 危险因素与大脑各个区域的 IgG 改变有关，这可能是由于体液免疫缺陷导致 IgG 介导的小胶质细胞清除 Aβ 受损，