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  4. Identification of Immune Cells and Key Genes associated with Alzheimer’s Disease

Identification of Immune Cells and Key Genes associated with Alzheimer’s Disease

International Journal of Medical Sciences, 2022 · DOI: 10.7150/ijms.66422 · Published: January 1, 2022

ImmunologyNeurologyBioinformatics

Simple Explanation

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive decline and memory loss, with inflammation recognized as a significant contributor. This research identifies immune cell types and key genes associated with AD using bioinformatics analysis of prefrontal cortex transcriptomic data. The study used data from the Gene Expression Omnibus (GEO) database and methods like CIBERSORT and WGCNA to analyze immune cell composition and gene co-expression networks. LASSO and random forest models helped identify key genes related to AD and M1 macrophages. The findings indicate that immune infiltration in the prefrontal cortex of AD patients differs from healthy individuals, with M1 macrophages being the most relevant cell type. Ten key genes associated with AD and M1 macrophages were identified and validated.

Study Duration
Not specified
Participants
310 AD patients and 157 healthy controls
Evidence Level
Not specified

Key Findings

  • 1
    Immune infiltration in the prefrontal cortex of AD patients differs from healthy samples, highlighting alterations in the brain's immune environment during AD.
  • 2
    M1 macrophages are identified as the most relevant immune cell type associated with AD, suggesting a critical role in the disease's pathology.
  • 3
    Ten key genes (ARMCX5, EDN3, GPR174, MRPL23, RAET1E, ROD1, TRAF1, WNT7B, OR4K2, and ZNF543) are identified as associated with AD and M1 macrophages, offering potential therapeutic targets.

Research Summary

This study investigates the role of immune cells and genes in Alzheimer's Disease (AD) by analyzing transcriptomic data from the prefrontal cortex of AD patients and healthy controls. The analysis reveals altered immune infiltration in AD patients, with M1 macrophages identified as a key cell type. Ten key genes associated with M1 macrophages and AD are identified through LASSO and random forest models. The identified genes are validated using independent datasets and transgenic mice models, providing potential therapeutic targets for AD.

Practical Implications

Therapeutic Targets

The 10 identified key genes could serve as potential targets for developing new immunotherapies for AD.

Diagnostic Markers

The identified immune cell infiltration patterns and gene expression signatures could be used as diagnostic biomarkers for early AD detection.

Understanding AD Pathology

The study enhances our understanding of the role of the immune system in AD pathology, paving the way for novel research directions.

Study Limitations

  • 1
    Limited sample size from public databases may not fully represent the true pathological state.
  • 2
    Lack of in vivo and in vitro validation for the identified key genes.
  • 3
    The origin and specific relationship of M1 macrophages with AD requires further investigation.

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