The dynamics of monocytes and microglia in Alzheimer’s disease

Peter Thériault, Ayman ElAli, Serge Rivest

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting older people worldwide. It is a progressive disorder mainly characterized by the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles within the brain parenchyma. It is now well accepted that neuroinflammation constitutes an important feature in AD, wherein the exact role of innate immunity remains unclear. Although innate immune cells are at the forefront to protect the brain in the presence of toxic molecules including Aβ, this natural defense mechanism seems insufficient in AD patients. Monocytes are a key component of the innate immune system and they play multiple roles, such as the removal of debris and dead cells via phagocytosis. These cells respond quickly and mobilize toward the inflamed site, where they proliferate and differentiate into macrophages in response to inflammatory signals. Many studies have underlined the ability of circulating and infiltrating monocytes to clear vascular Aβ microaggregates and parenchymal Aβ deposits respectively, which are very important features of AD. On the other hand, microglia are the resident immune cells of the brain and they play multiple physiological roles, including maintenance of the brain's microenvironment homeostasis. In the injured brain, activated microglia migrate to the inflamed site, where they remove neurotoxic elements by phagocytosis. However, aged resident microglia are less efficient than their circulating sister immune cells in eliminating Aβ deposits from the brain parenchyma, thus underlining the importance to further investigate the functions of these innate immune cells in AD. The present review summarizes current knowledge on the role of monocytes and microglia in AD and how these cells can be mobilized to prevent and treat the disease.