Landscape of immune infiltration in entorhinal cortex of patients with Alzheimer's disease

Hui Zhang; Silu Cao; Yaru Xu; Xiaoru Sun; Miaomiao Fei; Qi Jing; Xiaodong Xu; Jinxuan Tang; Bing Niu; Cheng Li

doi:10.3389/fphar.2022.941656

Landscape of immune infiltration in entorhinal cortex of patients with Alzheimer's disease

Front Pharmacol. 2022 Sep 28:13:941656. doi: 10.3389/fphar.2022.941656. eCollection 2022.

Authors

Hui Zhang^{1

2

3

4

5}, Silu Cao^{1

2

3

4

5}, Yaru Xu^{1

2

3

4

5}, Xiaoru Sun^{1

2

3

4}, Miaomiao Fei^{1

2

3

4}, Qi Jing^{1

2

3

4

5}, Xiaodong Xu^{1

2

3

4

5}, Jinxuan Tang^{1

2

3

4}, Bing Niu⁶, Cheng Li^{1

2

3

4}

Affiliations

¹ Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai, China.
³ Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Clinical Research Center for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, China.
⁵ Department of Anesthesiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
⁶ School of Life Sciences, Shanghai University, Shanghai, China.

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.

Keywords: Alzheimer’s disease; drug; entorhinal cortex; immune; transcriptomic.