New research has unveiled a fascinating connection between blood leakage into the brain and the activation of harmful genes in microglia, immune cells that reside in the brain (Figure 1). This activation transforms microglia into toxic cells capable of wreaking havoc on neurons, thereby leading to cognitive dysfunction and motor impairments observed in neurological diseases like Alzheimer’s and multiple sclerosis. Even in individuals without dementia, these microglia can contribute to age-related cognitive decline. Consequently, researchers have been diligently seeking to understand the triggers responsible for this transformation, as deciphering the exact mechanisms involved could open doors to novel treatments for various neurological disorders.
The recent study has pinpointed fibrin, a blood protein known for its role in blood clotting, as the culprit behind the activation of detrimental genes in microglia. Surprisingly, this effect was observed not only in Alzheimer’s disease but also in multiple sclerosis. The discovery suggests that by counteracting the blood toxicity caused by fibrin, it may be possible to safeguard the brain against harmful inflammation and neuronal loss commonly seen in neurological diseases.
Importantly, this study provides a comprehensive understanding of how blood leakage into the brain manipulates the brain’s immune system, resulting in toxic effects during brain diseases. Unraveling the intricate relationship between blood and the brain holds significant potential for the development of innovative treatments targeting neurological conditions.
Additionally, the researchers found that different blood proteins activate distinct molecular processes within microglia. Of all the proteins tested, fibrin stood out as the primary driver of gene and protein activities that render microglia toxic to neurons. The other blood proteins examined did not exhibit the same toxic effects.
The implications of these findings extend beyond specific diseases, as the mechanisms elucidated in this study could be relevant to a broad range of neurological conditions involving blood leaks in the brain. This includes neurodegenerative disorders, autoimmune diseases, stroke, and traumatic brain injury, highlighting the potential for these discoveries to impact diverse areas of neurological research and treatment development.
Journal article: Mendiola, A. S., et al. 2023. Defining blood-induced microglia functions in neurodegeneration through multiomic profiling. Nature Immunology.
Summary by Stefan Botha