Infections and Alzheimer’s disease risk

We often get asked if certain viruses, bacteria or fungal infections can cause Alzheimer's disease. This is because there is some research to show Alzheimer's is more common in people who have these infections. However, it is not yet clear whether these infections might trigger Alzheimer's or cause it to get worse. It could be that people with Alzheimer's are more susceptible to picking up infections.

Age is the biggest risk factor for the most common form of Alzheimer's disease. The immune system changes with age, so older people are also more susceptible to infections. However, some infectious conditions like pneumonia are more common in people with Alzheimer's than in healthy people of the same  age. Some of the infections that are thought to be linked to Alzheimer's include: oral herpes,  pneumonia and  infection with spirochete bacteria  (the type which cause Lyme disease and some types of gum disease).  There have also been links between Alzheimer's disease and other infections that cause a long-term activation of the immune system, a process known as chronic inflammation. 

Herpes 

The oral herpes virus (herpes simplex virus 1 or HSV1) causes cold sores and it stays in the body for life, including in the brain. It's very common - most people will eventually get an HSV1 infection. Although it usually infects the body, it also has been found in the brains of people with Alzheimer's disease and healthy people. Evidence of herpes infection has been found in the parts of the brain that are particularly affected in Alzheimer's  disease. Some researchers have proposed that herpes could, under some circumstances, lead to inflammation in the brain and changes to brain cell function. This could then potentially trigger or worsen Alzheimer's. 

Herpes infection  in the brain appears to be more common in people with Alzheimer's disease who have a gene called ApoE4, which is known to increase the risk of Alzheimer's. One theory behind this is that ApoE4 increases the likelihood of the herpes virus moving from the body into the brain. This might be part of the reason that people with ApoE4 are at an increased risk of Alzheimer's, although there are likely to be several reasons for this. Some researchers suspect that ApoE4 allows more  virus particles to attach themselves to brain cells, making it easier to infect them.

Although herpes infections are for life, most of the time the virus is dormant and symptom-free. Population research suggests that it is only re-activation of the virus, such as during a cold sore flare up, which increases a person's risk  of developing Alzheimer's disease.

It is worth bearing in mind that there is no strong evidence that herpes virus infection actually causes Alzheimer's disease. The increased presence of the virus in the brain may be related to changes to the immune system due to Alzheimer's disease.  

Pneumonia 

Chlamydophila  pneumoniae is the bacteria that causes pneumonia and bronchitis. It usually infects the respiratory tract. However, it can also evade the immune system and remain as a chronic infection inside cells, including white blood cells. This is especially common in people over 60. The bacteria has been found inside the brain  cells of people with Alzheimer's disease. Its presence in the brain could cause inflammation , which could contribute to the underlying Alzheimer's disease mechanism. It's thought that the bacteria get into the brain along the olfactory  nerve, which transmits information about smells from the nose to the brain. 

A review  of several studies shows that the evidence about whether or not there is a link between Chlamydophila  pneumoniae infection and Alzheimer's disease is somewhat conflicting. Some studies have found a link, and other studies found no association. This may partially be because many of the studies have been quite small, making it harder to detect a significant relationship. Even though some studies suggest Chlamydophila  pneumoniae infection is associated with increased risk of Alzheimer's disease, it's not clear whether the infection itself affects the progression of the disease.

Spirochete bacteria 

Spirochetes are a type of bacteria that cause diseases like syphilis, Lyme disease and gum disease. We have known for a long time that, under certain conditions, some chronic spirochete infections such as syphilis can cause dementia. Chronic gum disease caused by spirochetes is also a risk factor for Alzheimer's disease, and the bacteria are significantly more common in the brains of people with Alzheimer's than those without the disease. 

However, looking at all the studies  that investigate the link between spirochete infection and Alzheimer's reveals mixed results. Some studies found a strong link and some studies did not. This could partially  be explained by the small size of the studies, or the varying sensitivity of the methods used to detect spirochete infection. 

Does Alzheimer's make the brain more susceptible to infection? 

The blood-brain barrier protects the brain by controlling what substances can pass from the blood into brain tissue. In Alzheimer's disease, the blood-brain barrier is damaged, particularly in the brain region affected by Alzheimer's.

Evidence  suggests that inflammation, the Alzheimer's hallmark amyloid protein and the ApoE4 gene, which are all linked to Alzheimer's disease, can contribute to the breakdown of the blood-brain barrier. Once it has been weakened, bacteria, viruses, and other harmful substances can get through into the brain more easily. This may explain why certain viruses and bacteria, such as herpes and spirochetes, are more common in the brains of people with Alzheimer's.

How could inflammation caused by infections contribute to Alzheimer's?

If infectious bacteria, viruses or fungi reach the brain they can activate special immune cells in the brain called microglia. When microglia are activated, they can cause inflammation in the brain. This type of inflammation is thought to be involved in the progression of dementia by causing nerve cell death. 

There is also some evidence that inflammation in the body caused by chronic infections like gum disease can cause inflammation in the brain. Because the blood-brain barrier of people with Alzheimer's is leakier than normal, one theory is that active immune cells and the substances involved in the body's inflammatory response can get through into the brain.  This causes the brain's own immune cells to activate, leading to inflammation and possibly death of brain cells. Brain inflammation can also make the blood-brain barrier even leakier, allowing more of the body's immune cells through and starting a vicious cycle of damage. 

One other possible explanation for the link between these infections and increased risk of Alzheimer's comes from laboratory studies. These studies have found that in some lab-grown brain cells, herpes, pneumonia and spirochete infections can trigger production of the hallmark clumps of amyloid protein. These amyloid clumps cause damage to nerve cells, and are a hallmark of Alzheimer's disease. Amyloid has also been found to damage or kill several different germs. It's possible that brain cells originally release amyloid to try and protect themselves from these harmful invaders, but then it builds up into plaques. 

Could treating infections prevent or treat Alzheimer's? 

If the theory that infections can contribute to the development of Alzheimer's disease is correct, then treating the infections could help to prevent or treat Alzheimer's. 

Antibiotics and anti-viral drugs that treat some of these infections are starting to be tested in clinical trials of people with Alzheimer's disease. However, so far their results are inconsistent. One trial giving people with mild to moderate dementia a combination of antibiotics found they had smaller decline in thinking abilities compared to people who were not taking the drugs. However, another  trial of the same antibiotics in people with Alzheimer's did not find they had any effect on thinking abilities.

At the moment, there is not enough evidence to know whether treating infections would be a good strategy to treat Alzheimer's or to reduce the risk of the condition. Given that the immune system is thought to be a key factor in the development of the condition, further research is needed to shed more light on this important topic.