Alzheimer’s disease (AD) represents one of the main forms of dementia that afflicts our society. The expression of several genes has been associated with disease development. Despite this, the number of genes known to be capable of discriminating between AD patients according to sex remains deficient. In our study, we performed a transcriptomes meta-analysis on a large court of brains of healthy control subjects (n = 2139) (NDHC) and brains of AD patients (n = 1170). Our aim was to verify the brain expression levels of CHI3L2 and its correlation with genes associated with microglia-mediated neuroinflammation (IBA1), alteration of the blood–brain barrier (PECAM1), and neuronal damage (CALB1). We showed that the CHI3L2, IBA1, PECAM1, and CALB1 expression levels were modulated in the brains of patients with AD compared to NDHC subjects. Furthermore, both in NDHC and in AD patient’s brains, the CHI3L2 expression levels were directly correlated with IBA1 and PECAM1 and inversely with CALB1. Additionally, the expression levels of CHI3L2, PECAM1, and CALB1 but not of IBA1 were sex-depended. By stratifying the samples according to age and sex, correlation differences emerged between the expression levels of CHI3L2, IBA1, PECAM1, and CALB1 and the age of NDHC subjects and AD patients. CHI3L2 represents a promising gene potentially involved in the key processes underlying Alzheimer’s disease. Its expression in the brains of sex-conditioned AD patients opens up new possible sex therapeutic strategies aimed at controlling imbalance in disease progression.

阿尔茨海默病 (AD) 是困扰我们社会的痴呆症的主要形式之一。几种基因的表达与疾病的发展有关。尽管如此，已知能够根据性别区分 AD 患者的基因数量仍然不足。在我们的研究中，我们对健康对照受试者 ( n  = 2139) (NDHC) 和 AD 患者的大脑 ( n = 1170）。我们的目的是验证 CHI3L2 的大脑表达水平及其与小胶质细胞介导的神经炎症 (IBA1)、血脑屏障改变 (PECAM1) 和神经元损伤 (CALB1) 相关基因的相关性。我们发现，与 NDHC 受试者相比，AD 患者大脑中的 CHI3L2、IBA1、PECAM1 和 CALB1 表达水平受到调节。此外，在 NDHC 和 AD 患者的大脑中，CHI3L2 表达水平与 IBA1 和 PECAM1 直接相关，与 CALB1 呈负相关。此外，CHI3L2、PECAM1 和 CALB1 的表达水平与 IBA1 无关。根据年龄和性别对样本进行分层，CHI3L2、IBA1、PECAM1和CALB1的表达水平与NDHC受试者和AD患者的年龄之间出现相关差异。CHI3L2 代表了一个有前途的基因，可能参与阿尔茨海默病的关键过程。它在有性别条件的 AD 患者大脑中的表达开辟了新的可能的性治疗策略，旨在控制疾病进展的不平衡。