INTERLEUKIN-1 EXPRESSION IN DIFFERENT PLAQUE TYPES IN ALZHEIMERS-DISEASE - SIGNIFICANCE IN PLAQUE EVOLUTION

The histologically apparent polymorphism of plaques containing beta-am yloid in Alzheimer's disease is thought to represent different stages in plaque evolution. beta-amyloid-immunopositive plaques were classifi ed according to the pattern of beta-amyloid distribution (diffuse vs d ense-core) and the presence or absence of dystrophic beta-amyloid prec ursor protein-immunopositive (beta-PPP+) neurites (neuritic vs non-neu ritic). The potential contribution of microglia-derived interleukin-1 (IL-1), an immune response cytokine that induces synthesis and process ing of beta-APP, to the possible sequential development of these plaqu e types was examined through determination of the number of IL-1 alpha (+) microglia associated with each of four identified plaque types. Di ffuse non-neuritic plaques had the least dense and most widely dispers ed beta-amyloid, did not exhibit beta APP(+) dystrophic neurites, but most (78%) contained activated IL-1 alpha(+) microglia (2 +/- 0.2/plaq ue; mean +/- SEM). Diffuse neuritic plaques had more dense, but still widely dispersed beta-amyloid, displayed a profusion of beta-APP(+) dy strophic neurites, and had the greatest numbers of associated activate d IL-1 alpha(+) microglia (7 +/- 0.8/plaque). Dense-core neuritic plaq ues 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 wer e devoid of both IL-1 alpha(+) microglia and beta-APP(+) dystrophic ne urites. 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. Our dat a indicate that activation of microglia with expression of IL-1 in Alz heimer's disease is required to drive the metamorphosis of diffuse non -neuritic beta-amyloid deposits to the characteristic and diagnostic n euritic plaques of Alzheimer's disease.