Investigating microglia’s role in Alzheimer’s pathology

Announcing a new article publication for BIO Integration journal. Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. Microglia, as central nervous system (CNS) resident macrophages, are key to AD pathology. Indeed, microglia aggregation around amyloid-β (Aβ) deposits is an AD hallmark.

Triggering receptor expressed on myeloid cells 2 (TREM2) regulates microglial function. TREM2 boosts microglial responses to AD pathologic damage, drives homeostatic activation, and modulates protective pathways.

Anti-human TREM2 agonist monoclonal antibody (hT2AB) serves as an alternative TREM2 ligand and has therapeutic potential in TREM2-mutant mouse models. This study combined single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to clarify hT2AB molecular and cellular mechanisms in improving AD and analyze microglial dynamics in hT2AB-treated groups during AD progression.

Key functional subpopulations and core biomarkers were identified through pseudo-time analysis, cell communication analysis, and transcription factors (TFs) with a focus on the differentiation process of microglia towards a therapeutic phenotype, providing a theoretical basis and potential targets for optimizing AD treatment.