Inflammation Beyond Amyloid: Immune Cell Contributions to Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to a decline in various aspects of cognition, synaptic function, and neuronal survival, making it the most prevalent cause of dementia worldwide. While the accumulation of amyloid-???? plaques and neurofibrillary tangles is a key pathological characteristic of AD, their roles do not comprehensively account for disease pathogenesis. Recent literature indicates the role of immune-related risk genes and innate immune response dysregulation such as complement activation, microglial and macrophage responses, natural killer (NK) cell dysfunction, and neutrophil-mediated inflammation in AD pathogenesis. In addition, the limitation of in vitro and in vivo models and inconsistent biomarker related data has hindered therapeutic progress for AD. However, novel immunomodulatory drugs targeting various signaling pathways have shown promising results. This review aims to provide comprehensive updated information on immune dysfunction in AD pathogenesis and the role of novel immunomodulatory therapies in managing this highly morbid and fatal disease.