Study identifies key microglial subpopulation regulated by TREM2 antibody as potential target for Alzheimer's treatment

Research reveals how a TREM2 agonist antibody guides microglia toward a protective state, identifying the C2 subpopulation as a key effector in Alzheimer's.

By: AXL Media

Published: Mar 2, 2026, 6:09 AM EST

Microglia and the TREM2 regulatory pathway

A new study published in the journal BIO Integration has shed light on the role of microglia, the resident macrophages of the central nervous system, in the progression of Alzheimer’s disease. Microglia are known to aggregate around amyloid-beta deposits, a defining hallmark of the condition. Central to their function is the Triggering Receptor Expressed on Myeloid Cells 2, or TREM2, which modulates how these immune cells respond to pathological damage. The research focused on an anti-human TREM2 agonist monoclonal antibody, known as hT2AB, which acts as a ligand to boost protective microglial responses.

Advanced transcriptomic analysis of brain immune cells

To understand the molecular mechanisms of hT2AB, the research team employed a combination of single-cell RNA sequencing and spatial transcriptomics. These high-resolution techniques allowed scientists to analyze microglial dynamics and identify specific functional subpopulations within the brain during the progression of Alzheimer’s. By using deconvolution analysis and pseudo-time modeling, the study mapped out how different groups of microglia differentiate and communicate, providing a theoretical basis for identifying potential therapeutic targets.

Identification of the C2 effector subpopulation

The analysis identified seven distinct microglial subpopulations, with one specific group, labeled C2, emerging as the key effector regulated by the hT2AB treatment. Researchers found that the C2 subpopulation acts as a critical "turning subpopulation" in the differentiation process. The study mapped two distinct trajectories of cell development, both originating from homeostatic states but extending in different directions. The trajectory associated with hT2AB treatment showed a clear transformation of microglia toward a protective phenotype, which is essential for mitigating the damage caused by neurodegeneration.