The dense-core plaques of Alzheimer’s disease are granulomas

Abstract

Dense-core plaques, whose centers contain highly polymerized and compacted aggregates of amyloid β peptides, are one of the two defining histopathological features of Alzheimer’s disease. Recent findings indicate that these plaques do not form spontaneously but are instead constructed by microglia, the tissue macrophages of the central nervous system. We discuss cellular, structural, functional, and gene expression criteria by which the microglial assembly of dense-core plaques in the Alzheimer’s brain parallels the construction of granulomas by macrophages in other settings. We compare the genesis of these plaques to the macrophage assembly of mycobacterial granulomas, the defining histopathological features of tuberculosis. We suggest that if dense-core plaques are indeed granulomas, their simple disassembly may be contraindicated as an Alzheimer’s therapy.