Roles of Cytokines in Alzheimer's Disease

Abstract

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic system that plays a pivotal role in the pathogenesis and progression of Alzheimer's disease (AD). Of particular focus are cytokines, a group of immune signaling molecules that facilitate communication among immune cells and contribute to inflammation in AD. Extensive research has shown that the dysregulated secretion of certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, and TNF-α) promotes neuroinflammation and exacerbates neuronal damage in AD. However, anti-inflammatory cytokines (IL-2, IL-3, IL-33, and IL-35) are also secreted during AD onset and progression, thereby preventing neuroinflammation. This review summarizes the involvement of pro- and anti-inflammatory cytokines in AD pathology and discusses their therapeutic potential.

Keywords: Alzheimer’s disease; cytokine; neuroimmune system; pro- and anti-inflammatory cytokines.

Figure 1

Crucial components of the neuroimmune system. The neuroimmune system comprises several crucial components: immune cells, such as resident CNS cells (e.g., microglia and astrocytes) and infiltrating peripheral immune cells (e.g., CD8+ T cells and natural killer (NK) cells); the glymphatic system, which comprises the perivascular space, CSF, and interstitial fluid; and cytokines, such as IL-33, TNF-α, and IL-6.

Figure 2

Interaction of cytokines involved in AD pathology. Proinflammatory cytokines (red box) and anti-inflammatory cytokines (blue box) in AD. Arrows indicate the induced effects.

Figure 3

Correlation between cytokines and AD pathologies. Cytokines and their interaction between AD pathologies, such as neuronal death and neuronal inflammation, impaired microglia clearance, and Aβ deposition.