The brain relies on specialized cells to maintain its balance and defend against threats. Among these are microglia, the brain’s immune system. They constantly survey the brain environment, ready to respond to injury or disease. A protein marker, CD68, is often associated with these cells, indicating their activity and involvement in various brain processes.
Microglia: The Brain’s Immune Guardians
Microglia are immune cells found throughout the brain and spinal cord. They are the central nervous system’s primary active immune defense. These cells are highly dynamic, continuously monitoring the brain’s environment for pathogens, damaged cells, or debris.
In a healthy brain, microglia adopt a branched shape. Their functions extend beyond immune defense, maintaining brain homeostasis. This includes clearing cellular debris, removing unnecessary synapses (synaptic pruning), and supporting neuron health. Microglia also regulate neurotransmitter levels and communicate with other brain cells, contributing to overall brain function.
CD68: A Marker of Microglial Activity
CD68 is a protein whose expression significantly increases when microglia become activated, though it is present at low levels in resting microglia.
Elevated CD68 on microglia strongly indicates their activation, particularly during phagocytosis. Phagocytosis is the process where cells engulf and clear cellular debris, damaged cells, or foreign substances. CD68 is therefore used in research as a marker for activated, phagocytic microglia. While microglial activation, marked by increased CD68 expression, can be beneficial for clearing harmful substances, sustained or excessive activation can contribute to neuroinflammation.
CD68 Microglia in Brain Health and Disease
Increased CD68 expression on microglia is a common observation in various neurological conditions that involve neuroinflammation or tissue damage.
Alzheimer’s Disease
In Alzheimer’s disease, CD68-positive microglia are often found surrounding amyloid plaques, a hallmark of the disease. Their role is complex; while involved in clearing damaged cellular material, high levels of CD68 can also be associated with impaired cognitive function.
Parkinson’s Disease
In Parkinson’s disease, activated microglia, including those expressing CD68, are present in post-mortem brain samples, particularly in the substantia nigra. Microglia can internalize and degrade alpha-synuclein, a protein that aggregates in the disease, but prolonged activation can also lead to the release of inflammatory molecules and reactive oxygen species that harm neurons.
Multiple Sclerosis (MS)
Multiple sclerosis (MS) involves changes in microglial activity, with CD68 being a marker used to assess their state. In MS lesions, microglia can adopt a pro-inflammatory phenotype, characterized by phagocytic-related markers like CD68, and are involved in myelin phagocytosis. However, microglia also have roles in remyelination and limiting inflammatory responses, indicating their dual nature in MS.
Stroke and Traumatic Brain Injury (TBI)
Following acute ischemic stroke, CD68-expressing microglia and macrophages are detected in the infarct lesion. These cells suggest a role in tissue repair. Similarly, in traumatic brain injury (TBI), microglia rapidly activate to clear cellular and molecular debris. While early activation can promote recovery, chronic activation of CD68-positive microglia in TBI can lead to sustained inflammation and further tissue damage.
The function of CD68-positive microglia can therefore be protective or detrimental, depending on the specific disease context and the duration of their activation.