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 (75th percentile), and low CHI3L1 and CHI3L2 expression group (25th 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.

Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

Department of Biomedical and Biotechnological Sciences Anatomy Histology and Movement Sciences Section School of Medicine University of Catania Catania Italy

Department of Neurodegenerative Disease UCL Institute of Neurology London UK

Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Translational Stem Cell Biology Research Institute of the Medical University of Varna Varna Bulgaria

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Neurologic Unit AOU Policlinico San Marco Department of Medical Surgical Sciences and Advanced Technologies GF Ingrassia University of Catania Catania Sicily Italy

UK Dementia Research Institute at UCL London UK

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