Alzheimer's disease (AD) is one of the most common forms of dementia with still unknown pathogenesis. Several cytokines and chemokines are involved in the pathogenesis of AD. Among the chemokines, the CXCR4/CXCL12 complex has been shown to play an important role in the pathogenetic development of AD.

We investigated the expression levels of CXCR4 / CXCL12 in fifteen brain regions of healthy non-demented subjects (NDHC) (2139 sample) and AD patients (1170 sample) stratified according to sex and age. Furthermore, we correlated their expressions with the Neurogranin (NRGN) and CHI3L1 levels, two inflamm-aging markers.

We highlighted that CXCR4 gene expression levels were age-correlated in the brain of NDHC subjects and that AD nullified this correlation. A similar trend, but diametrically opposite was observed for CXCL12. Its expression was decreased during the aging in both sexes, and in the brains of AD patients, it underwent an inversion of the trend, only and exclusively in females. Brains of AD patients expressed high CXCR4 and CHI3L1, and low CXCL12 and Neurogranin levels compared to NDHC subjects. Both CXCR4 and CXCL12 correlated significantly with CHI3L1 and Neurogranin expression levels, regardless of disease. Furthermore, we showed a selective modulation of CXCL12 and CXCR4 only in specific brain regions.

Taken together our results demonstrate that CXCL12 and CXCR4 are linked to Neurogranin and CHI3L1 expression levels and the relationship between postsynaptic damage and microglial activation in AD could be shown using all these genes. Further confirmations are needed to demonstrate the close link between these genes.

阿尔茨海默病 (AD) 是最常见的痴呆症之一，其发病机制尚不清楚。多种细胞因子和趋化因子参与 AD 的发病机制。在趋化因子中，CXCR4/CXCL12 复合物已被证明在 AD 的发病机制中起重要作用。

我们研究了CXCR4/CXCL12在健康非痴呆受试者 (NDHC)（2139 个样本）和 AD 患者（1170 个样本）的 15 个大脑区域中的表达水平，这些区域根据性别和年龄分层。此外，我们将它们的表达与神经颗粒蛋白( NRGN ) 和CHI3L1水平相关联，这两种炎症衰老标志物。

我们强调 CXCR4 基因表达水平在 NDHC 受试者的大脑中与年龄相关，而 AD 抵消了这种相关性。CXCL12 观察到类似的趋势，但截然相反。它的表达在两性中随着年龄的增长而下降，并且在 AD 患者的大脑中，它的趋势发生了逆转，仅在女性中发生。与 NDHC 受试者相比，AD 患者的大脑表达了高 CXCR4 和 CHI3L1，以及低 CXCL12 和 Neurogranin 水平。无论疾病如何，CXCR4 和 CXCL12 都与 CHI3L1 和 Neurogranin 表达水平显着相关。此外，我们仅在特定大脑区域显示了 CXCL12 和 CXCR4 的选择性调节。

综上所述，我们的结果表明CXCL12和CXCR4与神经颗粒素和CHI3L1 的表达水平相关，并且可以使用所有这些基因显示 AD 中突触后损伤和小胶质细胞激活之间的关系。需要进一步的确认来证明这些基因之间的密切联系。