The histologically apparent polymorphism of plaques containing beta-amyloid in Alzheimer's disease is thought to represent different stages in plaque evolution. beta-amyloid-immunopositive plaques were classified according to the pattern of beta-amyloid distribution (diffuse vs dense-core) and the presence or absence of dystrophic beta-amyloid precursor protein-immunopositive (beta-APP+) neurites (neuritic vs non-neuritic). The potential contribution of microglia-derived interleukin-1 (IL-1), an immune response cytokine that induces synthesis and processing of beta-APP, to the possible sequential development of these plaque types was examined through determination of the number of IL-1 alpha+ microglia associated with each of four identified plaque types. Diffuse non-neuritic plaques had the least dense and most widely dispersed beta-amyloid, did not exhibit beta-APP+ dystrophic neurites, but most (78%) contained activated IL-1 alpha+ microglia (2 +/- 0.2/plaque; mean +/- SEM). Diffuse neuritic plaques had more dense, but still widely dispersed beta-amyloid, displayed a profusion of beta-APP+ dystrophic neurites, and had the greatest numbers of associated activated IL-1 alpha+ microglia (7 +/- 0.8/plaque). Dense-core neuritic plaques had both compact and diffuse beta-amyloid and had fewer IL-1 alpha+ microglia (4 +/- 0.4/plaque). Dense-core, non-neuritic plaques had compact beta-amyloid, lacked associated diffuse beta-amyloid, and were devoid of both IL-1 alpha+ microglia and beta-APP+ dystrophic neurites. These results suggest an important immunological component in the evolution of amyloid-containing plaques in Alzheimer's disease and further suggest that IL-1-expressing cells are necessary to initiate dystrophic neurite formation in diffuse beta-amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS)