Often scientists claim to make breakthrough discoveries, while their "findings" are known for many years. This is unsettling for lay persons as most of us, as it questions the real value of scientific publications. Here is another example, it has been known at least for 15 years that microglia phagocytes synapses that this process is mediated with the protein MFG-E8 and that this process is dysregulated in Alzheimer's disease.
Now scientists are claiming to just have discovered that and their publication was accepted in a prestigious journal.
Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive decline and the presence of abnormal protein aggregates in the brain, namely amyloid-β (Aβ) plaques and phosphorylated tau tangles. The accumulation of toxic forms of Aβ and tau contributes to synaptic loss, which is a major factor in AD-related cognitive decline. However, there are currently no effective treatments to prevent synapse degeneration in humans.
Recent research suggests that glial cells in the brain, specifically astrocytes and microglia, play a role in the removal of synapses, a process known as synaptic pruning.
Microglial cells are the main innate immune cells in the complex cellular structure of the brain. These cells respond rapidly to pathogens and injury and accumulate in regions of neurodegeneration, producing a wide variety of inflammatory mediators. Microglia respond to each disruption of homeostasis by rapidly changing form and function. The main physiological function of microglial cells is phagocytosis.
Microglia can adopt multiple phenotypes with unique characteristics depending on their environment. However, the M1 and M2 phenotypes are the most studied to date. The M1 phenotype is considered pro-inflammatory and represents the first line of defense of the innate immune system. Alternatively, M2 microglia are considered anti-inflammatory, with potential functions in tissue repair and remodeling. Microglial involvement has been implicated in many diseases like schizophrenia, Parkinson's disease, Alzheimer's disease, prion diseases and multiple sclerosis.
The study examined human brain tissue from individuals with AD and found that astrocytes and microglia contained more synaptic material in AD brains compared to healthy controls. This effect was more pronounced near Aβ plaques and in individuals with the APOE4 risk gene. In laboratory cultures, both mouse and human glial cells ingested synapses from AD patients more than those from healthy individuals. Inhibiting the interaction of a protein called MFG-E8 reduced this excessive synapse removal by glial cells, suggesting a potential target for therapy.
A milk membrane glycoprotein, MFG-E8 [milk fat globule-EGF (epidermal growth factor) factor 8], is expressed abundantly in lactating mammary glands. But as most of the time with proteins, it has multiple roles. In the peripheral immune system, macrophages secrete Milk Fat Globule Factor-E8 (MFG-E8) that recognizes phosphatidylserine "eat me" signals expressed on the surface of apoptotic cells. MFG-E8 then acts as a tether to attach the apoptotic cell to the macrophage and trigger a signaling cascade that stimulates the phagocyte development, allowing the macrophage to engulf the dying cell. When this process becomes disrupted, inflammation and autoimmunity can result. MFG-E8 resides in the brain as well as in the periphery, and microglia express MFG-E8.
The findings suggest that glial cells in AD patients may be responsible for the excessive removal of synapses, which is associated with cognitive decline. This insight could lead to the development of treatments aimed at preserving healthy synapses in AD patients, potentially improving cognitive function.