Humans have two immune systems, one for the body and one for the brain. The body’s immune system is its white blood cells which are generated from bone marrow. The brain immune system is composed of Glia cells, also generated from bone marrow during embryonic development of the brain. Immune systems function as protection against foreign invaders and correction of anomalies. This article focuses on the brain’s immune system.
The immune systems respond to anomalies which can be from injury or a foreign invader (antigen). Drugs have been developed to assist the immune system in correcting anomalies. Recreational drugs have highlighted addiction problems which impede the immune system capability to correct anomalies. Could it be the same for medical drugs?
Brain’s Immune System
Microglia are the brain’s immune system’s cells that are mobilized to present antigens and become phagocytes during injury, infection, and degenerative diseases. Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Microglia are stem cells and therefore, reproduce as needed in the brain. About 80% of all cells in the brain are microglia.
There are three main types of microglia: oligodendrocytes, Schwann cells, and astrocytes. Of these about half are oligodendrocytes and half are astrocytes. The oligodendrocytes and astrocytes are the principal cells in the central part of the brain and Schwann cells in the peripheral areas. The oligodendrocytes and Schwann cells produce a myelin insulation around axons and a protection as the brain blood barrier (BBB).
The astrocytes first appeared during embryonic brain development where they function as a guide for neurons to their brain location. Later, they control of extracellular ion and neurotransmitters concentrations and actively participate in the formation and function of synapse. All astrocyte functions are still unknown and a mystery, but astrocytes are receiving attention. AD laboratory research is using both genetics and big data models as well as animal models to attain greater knowledge of microglia roles in the immune system.
The Brain’s Immune System and AD
A report from Seyfriend et al., 2017 tracked alterations in how individual proteins and networks of proteins were turned on or off in brain tissues. This multi-network analysis revealed protein and disease-specific pathways involved in the etiology (study of cause) , initiation, and progression of AD. The report identified 10 proteins correlated to both AD and asymptomatic volunteers, mainly associated with inflammation and microglia cells. Asymptomatic volunteers are people who have no cognitive or functional symptoms of AD but are high risk from heredity. Therefore, this finding that correlates to both AD and asymptomatic volunteers may provide proteins as markers to track for asymptomatic people.
Also, genetics led to the identification of relatively rare variants in the gene triggering receptor expressed on myeloid cells 2 (TREM2) that is now identified as a high risk for developing AD. TREM2 mutations increase the risk of neurodegenerative conditions, such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease. Evidence shows that the Tau protein correlates with cognitive decline symptoms in AD through the breakdown of microtubules within the axon. Could TREM2 and/or other immune system protein be playing a role in the microtubules breakdown? Is inflammation involved? If axon breakdown only disrupt communication, could new pathways develop as a repair mechanism? . Finding which TREM2 variant or inflammatory protein might be involved is the challenge facing researchers along with their pursuit for understanding the brain’s immune system.
Proteomics is the study of the proteome. A proteome is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. Network changes in the AD brain proteome, including those associated with early asymptomatic stages of disease, are just beginning to be explored as indicted by Seyfriend et. al. report above. Could identification of the brain’s immune system proteins provide biomarkers for tracking asymptomatic and presymptomatic amyloid trials?