Cytokine-induced reprogramming of human macrophages toward Alzheimer's disease-relevant molecular and cellular phenotypes in vitro.

ABSTRACT: Myeloid cells, including brain-resident microglia and peripheral macrophages, play key roles in neurodegenerative diseases such as Alzheimer's disease (AD). Studying their disease-associated states is limited by the lack of robust in vitro models. Here, we test whether a cytokine mix (interleukin [IL]-4, CSF1, IL-34, and transforming growth factor-β) reprograms human THP-1 macrophages toward AD-relevant phenotypes. This treatment induces significant transcriptomic changes, driving THP-1 macrophages toward a transcriptional state reminiscent of disease-associated microglia and lipid-associated macrophages (LAM), collectively referred to as DLAM. Transcriptome profiling reveals gene expression changes related to oxidative phosphorylation, lysosome function, and lipid metabolism. Single-cell

SUBMITTER: Podlesny-Drabiniok A 

PROVIDER: S-EPMC12335816 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature