The Gut and Alzheimer's: A Surprising Connection

✍🏻 Aoife Delany | Lead Clinical Information Designer & Scientific Writer at Teckro

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What is Alzheimer's Disease?🧠

Alzheimer's disease (AD) is a brain disorder that slowly damages memory, learning, thinking and organisational skills over time.

Over 55 million people worldwide suffer from dementia, with AD accounting for 60-70% of these cases. Changes in brain regions associated with memory can take place years before symptoms begin to appear. Abnormal protein accumulation is thought to cause the disease including proteins like amyloid, which build up around cells in the brain, and tau, which tangles in the brain cells.. This leads to healthy brain cells ceasing function, eventually resulting in brain cell death. The presence of toxic protein alone does not always cause AD. However, evidence suggests that chronic inflammation in the brain could pull the trigger.

How does inflammation impact the brain in AD? 🔥

Chronic activation of the brain's inflammatory immune response appears to worsen toxic protein buildup in the brain.

After an injury or exposure to a harmful chemical or pathogen (bacteria, viruses etc.), the body activates the immune system by temporarily releasing inflammatory cells and chemicals to defend and heal. When toxic amyloid beta and tau proteins begin to accumulate in the brain, the body mounts an immune response to clear them. Brain-specific immune cells known as microglia are released to engulf and eat any foreign substances or pathogens that may cause the brain harm.

Video Credit: Hybrid Medical https://www.youtube.com/watch?v=aTs325_aCew

These immune cells migrate to accumulated protein to remove it. The immune cells become enlarged, and after a sustained period of time, are no longer able to process toxins. More microglia are subsequently recruited in an effort to clear the plaques, resulting in cell build-up in the areas with the original protein accumulation. Sadly, these efforts only encourage further toxic protein deposits. The immune system is caught in a loop whereby the inflammatory response is stuck in the 'on' position causing the chronic inflammation and protein accumulation that triggers AD. Our best friend has now become an enemy.

While microglia may act in the brain, the gut plays a crucial role in regulation and maturation of these vital cells.

How is the brain linked to the gut?🍎

The gut microbiome helps us in many way by being involved in digestion, immunity and even brain function.

The gut and the brain are intimately linked via the gut-brain axis. The gut-brain axis is a two-way communication network that connects the brain to the enteric nervous system in the gut (the part of the nervous system that governs the gastrointestinal tract- often described as the 'gut brain' or "the second brain"). Our gut is home to a wide variety of microorganisms such as bacteria, parasites, fungi and viruses, collectively referred to as the gut microbiome. For the most part, these microorganisms live in harmony with us, interacting with the body and assisting with functions such as digestion, immunity and even hormone release and regulation.

In recent years, there has been increasing evidence to suggest that gut bacteria in particular can have an effect on the brain via the gut-brain axis. Studies suggest that they may influence social behaviour (especially in autism), mood and mental health, and neurological diseases. It's even been proposed that gut bacteria might make us crave or avoid certain foods to help them thrive!

How does the gut contribute to AD?🦠

Emerging evidence suggests that gut bacteria may be linked to inflammation in the brain of AD patients.

Alterations in gut bacteria and bacterial toxins have been reported in AD patients suggesting that they do contribute to the disease. In particular, gut bacteria play an important role in the regulation of microglia. Absence of certain microbes can lead to defects in microglia which can impact the brain's ability to clear toxic protein build-up. Moreover, imbalances in gut microbes can trigger inflammation that may abnormally activate the microglia, resulting in the brain inflammation observed in AD.

Much research has focused on how gut bacteria may exacerbate AD, however, there is also evidence to suggest that abnormal gut bacteria may have a causal relationship with the disease.

Scientists in University College Cork (UCC) have recently induced AD in rats using gut bacteria. Patients with AD have a higher abundance of bacteria that promote inflammation in their gut. Fecal samples from AD patients containing these bacteria were transplanted into healthy young adult rats. After transplantation, the rats began to show signs of the disease such as impaired memory and decreased production of new brain cells, suggesting that alterations in gut bacteria could potentially trigger AD. This is further supported by mouse studies where germ-free mice (i.e., mice that have been bred without gut bacteria) show less signs of brain damage from toxic tau deposits and have lower levels of inflammation. Similarly, when antibiotics against certain bacterial strains were given to mice with a normal gut microbiome, male mice had reduced signs of brain inflammation (which begs further investigation given that almost two thirds of AD patients are female).

There will certainly be more researchers going with the gut for future AD investigations!

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Edited by: Olivia Laughton | Content Editor | BSc Microbiology, University of Leeds

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