Jack McKenna Jack McKenna20 September 2023 Open Science

Microglia’s Role in Neurodegenerative Disease is Complex

Microglia have a complex role in the brain, first working to prevent and then contributing to the development of neurodegenerative disease. They are known as the housekeepers of the brain, keeping it clear from debris and pathogens. But once this function stops working effectively, their processes have a negative effect.

Currently, dementia is the seventh leading cause of death worldwide, and rates are rising. Could microglia provide an avenue for helping us to understand neurodegenerative disease?

Here, we’ll explore microglia’s role in neurodegenerative diseases, beginning with where they fit in the brain’s structure.

The structure of the brain

The brain contains neurons. These are the brain’s messenger cells, which receive, transmit, and process information.

Far more numerous are non-neuronal cells called glia, which is a Greek word for glue. Glia work to support the functions of neurons. There are three types of glia, with the smallest being microglia. These make up 10% of the brain’s cells.

Microglia work to create a stable environment by keeping our brains clean and healthy.

Microglia’s role in the brain

In imaging studies, microglia appear to be very dynamic. In a steady state, they are constantly moving and have long branches that contact different cells and blood vessels and monitor the state of synapses.

Microglia are very crucial during the brain’s development. They help young neurons grow by ensuring the right connections are made and by performing “pruning”. This involves consuming the weaker or unnecessary connections between neurons whilst preserving the stronger ones.

Throughout your life, when events or agents like injuries or pathogens trigger inflammation, microglia change into larger, more-contained shapes and start replicating. This response enables them to effectively remove any unwanted material and induce neuroinflammation, which is inflammation of the brain, as part of the immune response.

Simply, microglia perform surveillance and maintenance of the brain, ensuring it develops correctly and is free from any matter that could disturb its stability. To do so, microglia trigger neuroinflammation, but over time this can contribute to neurodegenerative disease.

Alzheimer’s Disease

Neurodegenerative disease refers to diseases that primarily involve neuron loss, with symptoms reflecting which part of the brain is affected. Dementia is an umbrella term for the different diseases and conditions that cause cognitive loss. Alzheimer’s Disease is the most common cause for dementia, accounting for 60‒80% of cases.

Alzheimer’s Disease, which is primarily associated with memory loss, is believed to be caused by the build-up of two proteins: amyloid and tau. Amyloid build-up around brain cells is known as plaque, whilst tau form tangles within brain cells. These restrict the brain, decreasing its communication ability.

When functioning correctly, microglia help to prevent Alzheimer’s Disease. Let’s investigate how.

Microglia fighting Alzheimer’s Disease

As mentioned, Alzheimer’s Disease is thought to be triggered by the build-up of plaque and tangles in the brain. These cause blockages and reduce the ability of different parts of the brain to communicate.

Microglia trigger the process that helps to clear any build-ups or blockages. Microglia release proinflammatory substances that trigger the neuroinflammatory response. Then, they perform phagocytosis, which means they eliminate dead cells and any unwanted material, including the plaque and tangles.

Through life, this helps ensure the different parts of the brain function correctly and can continue communicating with each other. Neuroinflammation is therefore a crucial process for a healthy brain, and microglia’s role in neurodegenerative disease is at first preventative.

However, if neuroinflammation persists uncontrolled, it can cause negative effects. This is common in aging brains, which are always in a state of low-grade inflammation.

Neuroinflammation and Alzheimer’s Disease

Neuroinflammation is a double-edged sword. Over time, microglia’s ability to replicate and perform its functions decreases, meaning its ability to regulate inflammation worsens too. This is known as microglial dysregulation.

Most notably, studies have shown that chronic inflammation can lead to the production of plaques. This means that the microglia respond to plaque and tangles, which can be a trigger for them to produce more plaques. Therefore, as the microglia weaken, and more plaques and tangles form, the inflammation and build-up of blockages can work synergistically to trigger Alzheimer’s Disease development.

This contributes to the changing view that neuroinflammation is a cause rather than an effect of neurodegenerative disease, meaning it could provide a helpful indicator for diagnosing cases.

Microglia’s role in neurodegenerative disease

In summary, microglia play a key role in the developing brain by ensuring it is productive and well-connected. Throughout life, it performs a housekeeping role, triggering inflammation and removing any unwanted material.

However, as the brain ages, microglia’s proinflammatory response can become detrimental and worsen the progression of neurodegenerative diseases, including Alzheimer’s Disease.

Alzheimer’s Disease has no cure, and its burden is widespread, from the individual to the world at large. Microglia’s complex role in neurodegenerative diseases could provide an interesting avenue for clearing up the mysteries of these diseases and the brain itself.

If you’re interested in contributing to helping battle these diseases, why not contribute to an open access journal? MDPI makes all its research immediately available worldwide, giving readers free and unlimited access to the full text of all published articles. This means anyone can access and build upon your potentially life-saving research. See our full list of journals for more.

Fighting neurodegenerative disease is a global battle that will or already has affected everyone. Understanding it is key, and investigating microglia’s role in neurodegenerative disease could clear some of the uncertainty that surrounds it.

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