Landscape of immune infiltration in entorhinal cortex of patients with Alzheimerʼs disease

Abstract

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and manifests as progressive memory loss and cognitive dysfunction. Neuroinflammation plays an important role in the development of Alzheimer’s disease and anti-inflammatory drugs reduce the risk of the disease. However, the immune microenvironment in the brains of patients with Alzheimer’s disease remains unclear, and the mechanisms by which anti-inflammatory drugs improve Alzheimer’s disease have not been clearly elucidated. This study aimed to provide an overview of the immune cell composition in the entorhinal cortex of patients with Alzheimer’s disease based on the transcriptomes and signature genes of different immune cells and to explore potential therapeutic targets based on the relevance of drug targets. Transcriptomics data from the entorhinal cortex tissue, derived from GSE118553, were used to support our study. We compared the immune-related differentially expressed genes (irDEGs) between patients and controls by using the limma R package. The difference in immune cell composition between patients and controls was detected via the xCell algorithm based on the marker genes in immune cells. The correlation between marker genes and immune cells and the interaction between genes and drug targets were evaluated to explore potential therapeutic target genes and drugs. There were 81 irDEGs between patients and controls that participated in several immune-related pathways. xCell analysis showed that most lymphocyte scores decreased in Alzheimer’s disease, including CD4+ Tc, CD4+ Te, Th1, natural killer (NK), natural killer T (NKT), pro-B cells, eosinophils, and regulatory T cells, except for Th2 cells. In contrast, most myeloid cell scores increased in patients, except in dendritic cells. They included basophils, mast cells, plasma cells, and macrophages. Correlation analysis suggested that 37 genes were associated with these cells involved in innate immunity, of which eight genes were drug targets. Taken together, these results delineate the profile of the immune components of the entorhinal cortex in Alzheimer’s diseases, providing a new perspective on the development and treatment of Alzheimer’s disease.

GEO data mining identifies potential immune-related genes in hypertrophic scar and verities in a rabbit model

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BBB dysfunction drives neurotoxic myeloid cells in glioblastoma and Alzheimer’s disease

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Novel diagnostic biomarkers related to immune infiltration in Parkinson’s disease by bioinformatics analysis

“…A previous study revealed that some specific immune cells in brain tissue, including Treg cells, activated NK cells, and neutrophils, were significantly more or less abundant in patients with AD than in healthy controls (Hu and Wang, 2021), which is consistent with the results of this study. The infiltration levels of some immune cells, such as pDCs, macrophages, and basophils, were altered in the brain tissue samples of PD and AD patients compared to healthy controls (Qian et al, 2022;Zhang et al, 2022). The potential reasons for this were that the brain tissue samples were derived from different regions and that the pathological mechanisms of these two diseases are not completely the same.…”

“…Similarly, Alzheimer’s disease (AD), the most common neurodegenerative disease, is also closely related to immune infiltration ( Hu and Wang, 2021 ; Qian et al, 2022 ; Zhang et al, 2022 ). A previous study revealed that some specific immune cells in brain tissue, including Treg cells, activated NK cells, and neutrophils, were significantly more or less abundant in patients with AD than in healthy controls ( Hu and Wang, 2021 ), which is consistent with the results of this study.…”