Possible link between Alzheimer’s disease and gut microbiome found in mice – new study

Researchers may have found an unlikely contributor to the development of Alzheimer’s disease: the bacteria in your gut. Their study, published in the journal Science, suggested that certain gut bacteria increase the brain damage seen in mice with an Alzheimer’s-like disease.

In Alzheimer’s disease – the most common form of dementia – proteins build up abnormally in the brain. One of these proteins is called tau, and its build-up causes the death of brain cells that are involved in memory, causing forgetfulness and eventually permanent memory loss.

The researchers were working with a group of mice with a genetic mutation that causes the accumulation of tau protein in the brain. The mice were split into two groups: one group had a healthy gut microbiome (the collection of bacteria, viruses and fungi which live in the gut), while the other lacked a gut microbiome completely (these mice are nicknamed “germ free”). By the time they reached old age, the germ-free mice had significantly less brain damage caused by tau.

The germ-free mice also had a lower level of tau-associated inflammation in their brains. High levels of inflammation are seen in the brains of people with Alzheimer’s, contributing to brain damage. So the lower level of brain inflammation could be one of the reasons less brain damage was seen in these mice.

One of the main causes of Alzheimer’s-associated brain inflammation is the activation of a certain type of immune cell, known as microglia. Microglia are known to be regulated by the gut microbiome, which might explain why germ-free mice had lower levels of active microglia.

Removing the gut microbiome is not the solution

If you’ve heard of the gut microbiome, you might know that it is usually thought of as being important for our overall health. So the suggestion that not having a microbiome could reduce the severity of Alzheimer’s is surprising. However, if you’re wondering whether removing your gut microbiome might reduce your chances of developing the disease, you might be disappointed.

Everyone has a unique gut microbiome, which is home to millions of different types of bacteria, some of which are beneficial and some of which can be damaging to our health. One explanation for the study’s findings is that only a certain type of bacteria is involved in increasing brain inflammation and brain-cell death caused by tau.

The researchers tested this idea by dosing a third group of mice, which had a healthy gut microbiome, with antibiotics. The antibiotics reduced the level of inflammation in the brain, as well as the activation of microglia, although only in male mice. What’s interesting is that only certain types of gut bacteria were reduced by the antibiotics, so it might have been one of these bacteria that was helping cause brain damage in the mice.

It’s unclear why antibiotics only improved outcomes in male mice, but not females. In humans, Alzheimer’s disproportionately affects women. It’s not clear why, but research suggests that one reason women are at greater risk of Alzheimer’s could be the impact of hormone changes that occurs during menopause.

That the gut microbiome can affect the brain is unsurprising. Over a decade of research has revealed that there are strong communication links between the two, known as the gut-brain axis. The gut-brain axis helps regulate multiple bodily processes, including the immune system and, therefore, inflammation.

This is not the first study to have pointed to the role that the gut microbiome may have in developing Alzheimer’s disease in mice. There’s also evidence that the gut microbiome is different in people with Alzheimer’s disease compared to those who are healthy.

While the idea that the gut microbiome is linked to Alzheimer’s is compelling, it’s important to interpret the results of the study with caution. Mice, especially those with genetic mutations, are very different to humans. Their immune system, their genetics and, critically, their gut microbiome all have differences.

Germ-free mice also have an underdeveloped immune system. Their gut-brain axis is affected too, with research in germ-free mice showing changes to their behaviour and brain signalling compared with normal mice. These differences could also be a reason the germ-free mice in the study didn’t develop such severe Alzheimer’s.

Based on current research, it can’t be claimed that bacteria in the gut microbiome contribute to Alzheimer’s disease in humans. Instead, the research points to the possibility that there are specific bacteria within the gut microbiome that could increase the risk of developing Alzheimer’s. If it can be shown that there are similar bacteria in humans that have similar effects, the possibility that targeting them might form a new basis for treating Alzheimer’s is an exciting prospect.

Catherine Purse, PhD Candidate, Quadram Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Macular diseases cause blindness and treatment costs millions. Here is how to look after yours

The single most expensive drug for the Australian government today, costing more than A$400 million per year, is one called aflibercept. It stops the growth and “leakiness” of blood vessels, and is given to treat a range of different eye diseases. These diseases have one thing in common: they all affect a piece of tissue inside the eye called the macula.

The macula is a structure that distinguishes us humans, as well as some other primates including apes and monkeys. It is a part of the retina that lets us recognise people’s faces, navigate a car and read the newspaper. Our eye is built to focus images onto the macula to achieve this level of vision.

Like the rest of the retina, the macula consists of cells that detect light – photoreceptors – plus nerve cells and other supporting cells, but they are arranged differently to ensure images are seen in high resolution. The macula also contains the highest body concentration of yellow carotenoid pigments – protective antioxidants which filter out blue light to hone vision.

Scientists are working to understand why so many diseases and conditions, including diabetes, inflammation and parasitic infection, affect the macula. This is likely due to a host of factors: from the special anatomy of cells, to blood supply, the need for carotenoid pigments and a high metabolic rate.

The many causes of macular disease

When a person’s macula becomes diseased, they often experience changes in vision. However, because the macula is just one part of the retina, even severe macular disease generally does not cause complete loss of sight.

Dame Judi Dench has talked about her macular disease – macular degeneration – including how friends help her learn lines by repeating them over and over to her, and how fellow performers help her know where to face when she is acting. Having this condition might mean she no longer drives a car, but she continues to live a full life.

Macular degeneration affects about one in seven people over 50 years of age, and can occur as an overgrowth of blood vessels or as a loss of tissue.

Diabetes causes an accumulation of fluid in the macula, called macular oedema; around one in 15 people with diabetes develop this condition. Other causes of macular oedema include a blocked blood vessel or inflammation inside the eye. It can also be a complication after cataract surgery.

There are many more macular diseases.

Toxoplasmosis – a parasite infection – often affects the macula.

Macular disease is a side effect of some drugs, such as hydroxychloroquine used to treat inflammatory diseases like lupus, and the new immunotherapy drugs for cancers including melanoma.

Central serous chorioretinopathy is a macular disease that affects younger adults and is associated with high levels of the stress hormone cortisol. Rare inherited conditions can affect the macula even earlier in life.

Treatments and prevention: 5 ways

Treatments depend on the type of macular disease. Most drugs are given by injection with a fine needle into the back part of the eye, called the vitreous. This quick procedure may be done in the doctor’s office.

But understanding what the causes of disease have in common points to lifestyle changes that can protect the macula or slow the damage of diseases.

1. Diet

Researchers at the United States National Eye Institute have shown the benefits of a Mediterranean diet, heavy in legumes and other vegetables, fruits, nuts and whole grains, and favouring fish over red meat, for protection against macular degeneration. A supplement combining vitamin C and E, lutein and zeaxanthin, zinc and copper is also recommended to limit progression of certain types of degeneration.

2. Avoiding smoking

Not taking up smoking or quitting if you are already a smoker safeguards your macula. Smoking has been linked to a number of macular diseases, including macular oedema and central serous chorioretinopathy, as well as macular degeneration.

3. Sun smarts

Wearing a sunhat and sunglasses from childhood may have benefits beyond skin safety. Some studies suggest sunlight exposure is a risk factor for macular degeneration. Physical activity can also protect against this condition, although there is debate about whether vigorous exercise is protective or potentially dangerous.

4. Shut eye

Quality sleep protects the macula. Sleep apnoea is associated with several macular diseases, including macular degeneration, macular oedema and central serous chorioretinopathy. Moreover, people with these diseases and untreated sleep apnoea may need more frequent drug injections for their condition.

5. Busting stress if possible

Limiting stress in life is difficult, but stress is a well-established risk factor for central serous chorioretinopathy. One group of US researchers reported an unusually high number of people with the disease at their local health network early in the COVID pandemic, which was a highly stressful time.

Controlling other aspects of diseases that affect the macula can be important too. For example, the macula benefits from: keeping blood pressure well-controlled, stabilising blood sugars in people with diabetes, and reducing inflammation in people with uveitis.

Check it and see

You can monitor your own macula using a simple test called the Amsler grid, available for free online.

Testing with an Amsler grid picks up changes in the vision caused by macular diseases.

Self-testing doesn’t take the place of regular checks with your eye health practitioner. They can examine your macula directly, usually after dilating the pupils, and may employ a powerful technology – optical coherence tomography – to scan through it.

Justine R. Smith, Professor of Eye & Vision Health, Flinders University

This article is republished from The Conversation under a Creative Commons license. Read the original article.