Alzheimer's Disease is a slowly progressive illness of neuron loss leading to memory problems, cognitive impairment, and eventually death.   Since there appear to be no conventional medicine ways to prevent Alzheimer's and there is no known cure, there is a flurry of research trying to figure out what may cause the condition (besides genetics, which we can't do much about) and what might help the symptoms.

I've addressed some of this research in previous posts:

Alzheimer's and High Blood Sugar

Alzheimer's and Omega 3s

Dementia and Other Studies of How Saturated Fat is Good for You

Today, we will take a peek at one of the more compelling theories about the cause of Alzheimer's -- it may well be due to an infection. Meaning exposure to certain parasites, bacteria, or viruses, particularly those that tend to inhabit the central nervous system, could bring on the disease. Even if you don't find Alzheimer's that compelling, if infectious agents contribute to its pathology, then you have to open your mind to the idea that many neurodegenerative processes could be due to (or accelerated by) infection.  Neurodegenerative diseases include many neurological illnesses, but also depression, bipolar disorder, schizophrenia, autism, and some other psychiatric illness.

What is the argument against infection as an ongoing contributing factor?  Well, where's the bug? Do a spinal tap - does the fluid grow any bacteria in culture?  Are there white blood cells (sign of active infection)?  Is there an elevated level of protein (a sign of viral infection)?  Over the last hundred years we've become pretty good at finding bugs.  It's hard to imagine them hiding from us, even in the protected environment of the human skull.  So if you bring up the idea of infections causing Alzheimer's disease to a physician friend and he or she scoffs at you -- that's why.  Where's the bug?

With that in mind, let's plunge forward into a very good review by Urosevic and Martins from the Journal of Alzheimer's Disease, "Infection and Alzheimer's Disease: The Apoe epsilon4 Connection and Lipid Metabolism."

The whole theory is based on the following premise: there's a continuous, chronic infection supplying persistent live microorganisms, and their toxic products stimulate the host's (that's you) inflammatory response.  The pathogen itself damages the neurons, and the brain's inflammatory response also damages the neurons. 

ApoE4 is the  Alzheimer's vulnerable genetic variant of apolipoprotein. ApolipoproteinE is basically a molecular key that helps cholesterol and triglycerides go from the circulation into the brain. Since we know that being a carrier of ApoE4 makes one more likely to get Alzheimer's, any theory postulating an infectious origin of Alzheimer's will have to explain why ApoE4 will leave more vulnerable as well. Fortunately, the infectious theory meets that criteria, as you will see below.

What infectious agents are we talking?  Some viruses immediately come to mind, specifically herpes viruses.  These little guys are exceedingly common and come in lots of different flavors, and are well known to hide out in nerve cells for the duration of the host's life (an easy example of "There's the bug.")  HSVI, associated with cold sores, infects people early in life and hangs out in the trigeminal ganglia (the nerve root of the trigeminal nerve that innervates a good part of the face).  Some people get cold sores, some people don't, but those who do are more likely to be ApoE4 carriers.  People infected with HSVI are also more likely to develop Alzheimer's.  ApoE4 mice were more likely to carry invasive HSVI and have brain colonization of the virus.

Other viruses implicated include human herpes virus 6 (cause of roseola, a common childhood illness of high fever followed by a characteristic rash), HIV, hepatitis C, and cytomegalovirus (a cause of mononucleosis-like illness and fatigue symptoms).  It is well known that HIV causes a form of AIDS dementia (which happens to be more common in carriers of ApoE4), so it would make sense that other common viruses that infiltrate the neurons might lead to other types of dementia.

All the common inflammation players (TNFalpha, IL-6, nitric oxide synthase) are involved in fighting off viral infections.  We know these players have a role in Alzheimer's pathology and in depression and bipolar disorder.  Interestingly, as we get older, our immune response becomes less aggressive, and it is perhaps then that the infectious agents hold sway, leading to Alzheimer's pathology.  Other inflammation-mediated brain disease occurs at different developmental stages - late adolescence and early adulthood for schizophrenia, and infancy for autism.

In this very recent study of mice, scientists were able to inject the extracts of mouse brains from mice with Alzheimer's (or an experimental mouse version of it) into mice with no signs of Alzheimer's Over time, the injected mice began to develop plaques and mouse dementia, while mice that weren't injected didn't develop the problem.

There are also suspected bacterial causes.  The "spirochetes" are a type of sneaky bacteria that are known to infect nerves (as in syphillis and Lyme disease).  Some spirochetes that cause gum disease are found in the mouths of Alzheimer's patients and healthy folks, but in the Alzheimer's patients, they are found in the brain more often than in healthy folks.  Certain spirochetes have been found in the amyloid plaques in the brains of patients with Alzheimer's (once again - there's the bug).

Chlamydia pneumoniae is an intracellular bacterial pathogen also implicated in Alzheimer's dementia.  Not surprisingly, it is better known as a common cause of pneumonia and other acute respiratory infections, but infected immune cells could presumably carry Chlamydia pneumoniae from the upper respiratory tract to the brain if the blood brain carrier is compromised in some fashion.  Chlamydia pneumoniae has been injected into mouse brains and causes amyloid deposits, which anyone will agree is suspicious behavior.  Once again, ApoE4 comes up, as ApoE4 seems to allow for greater bacterial load and numbers of infected cells.

ApoE4 is not only a bad guy when it comes to Alzheimer's in the modern world.  Carriers are at greater risk of atherosclerosis, stroke, and poor recovery from head injury.  And ApoE's role as a molecular marker and director of where lipoproteins go is key.  Lipoproteins are how fat and antioxidants are carried throughout the body.  It is probably not a coincidence that major conditions leading to weight loss without any particular effort are infectious disease and Alzheimer's (along with cancer and melancholic depression).   ApoE4 in particular is associated with poor clearance and recycling of lipoprotein particles.  It's just not a very efficient key.  If everything is going along just fine, maybe we don't need a particularly efficient key.  Add stress or infection, though, and you have a greater need for metabolic efficiency.  If you fall behind on cleanup and recycling, garbage builds up in the brain, causing major problems.

The ability of a host (you, or me) to handle an infection depends on genetic, dietary, and other environmental factors such as age, stress, and immune status.  Viruses, parasites, and bacteria are sneaky - I daresay sneakier even than Homo sapiens, and the closeted nerve cells are a perfect place for an unnoticed infection to simmer for decades.  Microorganisms can continuously release toxins, leading to chronic inflammation and damage.  Treating a chronic infection and boosting a healthy immune system could possibly be a useful way to fight a number of neurodegenerative diseases, even Alzheimer's.

Image credit (also

Image Credit (TEM micrograph of HSV)

Copyright Emily Deans, MD

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