Effect of neuroinflammation on the progression of Alzheimer's disease and its significant ramifications for novel anti-inflammatory treatments

Abstract

Alzheimer's disease (AD) is increasingly recognized as a disorder not solely of amyloid and tau accumulation but also of chronic immune dysregulation. Emerging evidence highlights the critical role of neuroinflammation, characterized by sustained activation of microglia and astrocytes, cytokine release, and inflammasome activation in accelerating AD progression. Genome-wide studies have further identified key inflammatory genes and immune pathways associated with increased disease risk. This review critically evaluates the mechanistic underpinnings of neuroinflammation in AD, focusing on glial cell behavior, immune signaling, and their contribution to neuronal dysfunction. Importantly, the review highlights recent advances in anti-inflammatory therapeutic approaches, including modulators of IL-1β, TNF-α, TREM2, and CB2 pathways. By integrating mechanistic and therapeutic insights, this work underscores the potential of immunomodulatory strategies as viable interventions in AD and provides a novel framework for future research in targeted anti-neuroinflammatory treatments.

Keywords: Alzheimer’s disease; Anti-inflammatory therapy; Cytokines; Glial cells; Microglia; Neuroinflammation.

Graphical abstract

Fig. 1

Illustrates how amyloid, tau, cholinergic, and mitochondrial dysfunctions converge on neuroinflammation as a central pathological mechanism in Alzheimer’s disease.

Fig. 2

Different Hypotheses of AD.

Fig. 3

Role of cytokines in Alzheimer's disease (Ogunmokun et al., 2021a).

Fig. 4

Factors affecting neuroinflammation.