Alzheimer’s disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75^th percentile), and low CHI3L1 and CHI3L2 expression group (25^th percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation.

阿尔茨海默病 (AD) 是最常见的进行性失能性痴呆症。长期以来，几丁质酶 CHI3L1 和 CHI3L2 一直被认为是神经变性中小胶质细胞和星形胶质细胞激活的生物标志物。在这里，我们从国家生物技术信息中心 (NCBI) 的非痴呆对照 (NDC)（n = 460）和已故 AD 患者（n = 697）的大脑样本中收集了微阵列数据集。根据性别对 AD 患者进行分层。比较高 CHI3L1 和 CHI3L2 表达组（第 75^个百分位）和低 CHI3L1 和 CHI3L2 表达组（第 25 个^百分位）百分位数），我们根据患者的性别获得了八个特征，并使用属于十二个细胞群的神经免疫特征（NIS）进行了基因组反卷积分析。表达分析显示，与 NDC 相比，AD 中的 CHI3L1 和 CHI3L2 表达显着更高，并且这些基因与 GFAP 和 TMEM119 呈正相关。此外，去卷积分析表明，CHI3L1 和 CHI3L2 的高表达与两性的炎症特征相关。在具有低 CHI3L1 和 CHI3L2 表达水平的 AD 患者中，神经元激活特征被显着激活。此外，对两种几丁质酶调控的共同基因进行基因本体论分析，揭示了免疫反应是一个主要的生物过程。最后，小胶质细胞 NIS 与 CHI3L2 表达水平显着相关，与由 CHI3L1 确定的小胶质细胞 NIS 相似度超过 98%。根据我们的结果，AD 患者大脑中高水平的 CHI3L1 和 CHI3L2 与炎症转录组学特征相关。CHI3L1 和 CHI3L2 之间的高度相关性表明存在强烈的共同调节。