Microglial phagocytosis of amyloid-beta (Abeta) deposits is involved in Abeta clearance in vivo. To explore the ability of microglia to phagocytose beta, we cultured human microglia or human monocytic THP-1 cells directly on unfixed frontal cortex sections of an Alzheimer disease (AD) case. We found that when these cells were activated by lipopolysaccharide (LPS) plus interferon (IFN)-gamma, they developed ameboid morphology and formed clusters around and attaching to amyloid plaques in the tissue. Some cells adhering to these plaques internalized Abeta and some appeared to be degraded. Nevertheless, no significant reduction of the overall Abeta burden was observed. If the cells were not stimulated, they adhered poorly to the sections. We quantified THP-1 cell adhesion to an AD brain section compared with a normal brain section and found it to be significantly increased. If a brain section was rinsed with phosphate buffered saline containing 0.1% Triton X-100, most LPS/IFN-gamma-activated THP-1 cells failed to adhere. However, in co-culture with human astrocytes, the number of adherent THP-1 cells was significantly increased. These results suggest that human microglial cells are capable of adhering to and phagocytosing post mortem AD plaque material but activation may be necessary. Astrocytes may further enhance the process.