Integrated Transcriptomic and Spatial Analyses Associate M2-like Myeloid Signatures with Neuroimmune Remodeling in...

Area of Science:

• Neuroimmunology
• Genomics
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) features neurodegeneration and neuroinflammation.
• The role of myeloid cells, like macrophages, in AD progression is not fully understood.

Purpose of the Study:

• To characterize myeloid immune cell changes in Alzheimer's disease.
• To correlate these changes with disease severity and neuropathology.

Main Methods:

• Integrated bulk, single-cell, and spatial transcriptomic data.
• Analyzed myeloid cell signatures across different Braak stages.
• Utilized immune-feature classifiers and CellChat for interaction analysis.

Main Results:

• M2-like macrophage and myeloid signatures progressively enriched with AD severity.
• Associated pathways included macrophage proliferation and TGF-β signaling.
• Identified specific signaling contexts (ApoE, CX3C, FN1) involving M2-like myeloid cells.

Conclusions:

• M2-like myeloid programs are consistently associated with Alzheimer's disease severity.
• These myeloid signatures represent potential neuroimmune components for further validation.
• This study highlights the remodeling of neuroimmune networks in AD.