Interleukin-1 Expression in Different Plaque Types in Alzheimerʼs Disease

TLDR

Alzheimer’s disease plaques vary histologically, with β‑amyloid–positive plaques classified as diffuse or dense‑core and neuritic or non‑neuritic based on β‑amyloid distribution and dystrophic neurites. The study examined whether microglia‑derived IL‑1 contributes to the sequential development of different β‑amyloid plaque types by counting IL‑1α+ microglia associated with each plaque type. The authors quantified IL‑1α+ microglia around four plaque types to assess IL‑1’s role in plaque evolution. IL‑1α+ microglia were most abundant in diffuse non‑neuritic plaques (≈78 %) and increased with neuritic pathology, while dense‑core non‑neuritic plaques lacked IL‑1+ microglia, indicating that IL‑1 expression is required to initiate dystrophic neurite formation and drive the transition to neuritic plaques.

Abstract

The histologically apparent polymorphism of plaques containing β-amyloid in Alzheimer's disease is thought to represent different stages in plaque evolution, β-amyloid-immunopositive plaques were classified according to the pattern of β-amyloid distribution (diffuse vs dense-core) and the presence or absence of dystrophic β-amyloid precursor protein-immunopositive (β-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 β-APP, to the possible sequential development of these plaque types was examined through determination of the number of IL-1α+ microglia associated with each of four identified plaque types. Diffuse non-neuritic plaques had the least dense and most widely dispersed β-amyloid, did not exhibit β-APP+ dystrophic neurites, but most (78%) contained activated IL-1α+ microglia (2 ± 0.2/plaque; mean ± SEM). Diffuse neuritic plaques had more dense, but still widely dispersed β-amyloid, displayed a profusion of β-APP+ dystrophic neurites, and had the greatest numbers of associated activated IL-1±+ microglia (7 ± 0.8/plaque). Dense-core neuritic plaques had both compact and diffuse β-amyloid and had fewer IL-1±+ microglia (4 ± 0.4/plaque). Dense-core, non-neuritic plaques had compact β-amyloid, lacked associated diffuse β-amyloid, and were devoid of both IL-1α+ microglia and β-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 β-amyloid deposits. Our data indicate that activation of microglia with expression of IL-1 in Alzheimer's disease is required to drive the metamorphosis of diffuse non-neuritic β-amyloid deposits to the characteristic and diagnostic neuritic plaques of Alzheimer's disease.