Microglial Transforming Growth Factor-β Signaling in Alzheimer's Disease

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• Single-cell RNA and single-nucleus RNA sequencing reveal complex microglia heterogeneity.
• Transcriptomic profiling aids in subclassifying microglia in neurodegenerative diseases.
• Disease-associated microglia often show downregulated homeostasis and upregulated inflammatory markers.

Purpose of the Study:

• To review the complex interactions of key molecules in microglia during Alzheimer's disease.
• To highlight the role of apolipoprotein E, TREM2, and TGF-β in microglia regulation.
• To understand microglia's contribution to neurodegeneration.

Main Methods:

• Review of transcriptomic profiling data from single-cell and single-nucleus RNA sequencing studies.
• Analysis of gene expression patterns in murine and human microglia samples.
• Examination of the roles of Apolipoprotein E, TREM2, and TGF-β in microglia.

Main Results:

• Identification of specific disease-associated microglia clusters.
• Concordance observed in certain microglia clusters between murine and human samples.
• Apolipoprotein E strongly regulated in Alzheimer's disease-associated microglia clusters.
• Transforming growth factor-β influences microglia maturation, activation, and amyloid-beta deposition.

Conclusions:

• Apolipoprotein E, TREM2, and transforming growth factor-β interact in a regulatory axis within microglia.
• This axis plays a crucial role in the onset and progression of Alzheimer's disease.
• Understanding these interactions is vital for therapeutic strategies targeting neurodegeneration.