Alzheimer’s Disease: From Immune Homeostasis to Neuroinflammatory Condition

Abstract

Alzheimer’s Disease is the most common cause in the world of progressive cognitive decline. Although many modifiable and non-modifiable risk factors have been proposed, in recent years, neuroinflammation has been hypothesized to be an important contributing factor of Alzheimer’s Disease pathogenesis. Neuroinflammation can occur through the combined action of the Central Nervous System resident immune cells and adaptive peripheral immune system. In the past years, immunotherapies for neurodegenerative diseases have focused wrongly on targeting protein aggregates Aβ plaques and NFT treatment. The role of both innate and adaptive immune cells has not been fully clarified, but several data suggest that immune system dysregulation plays a key role in neuroinflammation. Recent studies have focused especially on the role of the adaptive immune system and have shown that inflammatory markers are characterized by increased CD4+ Teff cells’ activities and reduced circulating CD4+ Treg cells. In this review, we discuss the key role of both innate and adaptive immune systems in the degeneration and regeneration mechanisms in the pathogenesis of Alzheimer’s Disease, with a focus on how the crosstalk between these two systems is able to sustain brain homeostasis or shift it to a neurodegenerative condition.