The role of the immune system in driving neuroinflammation

Abstract

Neuroinflammation is now recognised as an important contributory factor in the progression of Alzheimer’s disease and probably also in the early stages of the disease. It is likely that this derives largely from aberrant activation of microglia, the resident mononuclear phagocytes of the brain. These cells are responsible for physiological immune surveillance and clearance of pathogens in the central nervous system, but evidence indicates that in Alzheimer’s disease, microglial function is compromised, and this contributes to the pathology. It is unclear what factors cause the inappropriate activation of the microglia in Alzheimer’s disease, but one contributor may be infiltrating peripheral immune cells and these include macrophages and T cells. It has been suggested that both cell types modulate the phenotype of microglia, highlighting the importance of crosstalk between the innate and adaptive immune system in Alzheimer’s disease. This review outlines our current knowledge of how cells of the peripheral immune system, specifically macrophages and T cells, may modulate microglial phenotype in the context of Alzheimer’s disease and considers the impact on their function, especially phagocytic capacity.

Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly

“…Other researchers have posited additional potential mechanisms for COVID-related neuroinflammation including cytokine network dysregulation, peripheral immune cell transmigration and a post infection aberrant autoimmune response. 9 ] Two of the four patients in this report had Alzheimer's disease (AD) and neuroinflammation is increasingly being recognized as an important factor in the progression of AD 16,17 and may link late life depression, mild cognitive impairment, and AD. 18 The clinical profiles of demented patients infected with the COVID-19 virus are just beginning to be examined.…”

Novel Blood-Derived Extracellular Vesicle-Based Biomarkers in Alzheimer’s Disease Identified by Proximity Extension Assay

“…The peripheral immune system has been shown to be implicated in AD pathology, with infiltration of immune cells, e.g., macrophages to aid microglia with phagocytosis of Aβ [ 55 ], and cells of the immune system release EVs into the circulation [ 56 ]. Several of the FDR significant proteins have also been associated with immune cells, some of them such as Siglec-9 with neutrophils and monocytes [ 57 ], CLM-6 with monocytes and T cells [ 47 , 48 ], and CLM-1 and CCL11 with eosinophils [ 53 , 58 ].…”

Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder

“…Inflammation of the nervous system, commonly known as neuroinflammation, can be characterized by the activation of microglia (which play a role in pathological and physiological conditions), astrocytes, oligodendrocytes, and ependymal cells, by increasing levels of proteases, glutamate, ROS, NO, chemokines, toxic cytokines, and prostaglandins and by infiltration of T and B cells, neutrophils, monocytes/macrophages and dendritic cells [ 96 , 97 , 98 , 99 ]. The role of neuroinflammation has been associated with several neuropsychiatric disorders, such as autism [ 100 ], bipolar disorder [ 101 ], depression [ 102 ], and schizophrenia [ 103 ].…”