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Spread Theory Extended to Alzheimer's Disease, Atherosclerosis and Diabetes



Could our whole theory of the most common causes of death be wrong?

In recent decades, public health has moved from infectious diseases to lifestyle. Now that we've mastered plagues like tuberculosis, pneumonia and cholera, the story says we need to focus on exercise and diet. With a little more self-discipline, we could avoid heart disease, cancer, diabetes and perhaps even Alzheimer's disease.

But what happens if these killers turn out to be old – caused, at least in part, by pathogens? This is not a new idea, and it stays out of the mainstream. But proponents argue that the recent findings deserve much more attention than they have received.

"The evidence is gradually accumulating that these conditions are infection-related, yet government agencies, such as the US National Institutes of Health, provide virtually no funding." [to research this topic]Says Richard Lathe, PhD, DSc, Honorary Professor of Biology at the University of Edinburgh, Scotland.

All three diseases become more common with age, and a person with one of these diseases is at increased risk for others.

If this is confirmed, the paradigm of the pathogen could lead to new treatments, perhaps revolutionizing how the most common diseases are managed. And this could help explain why seemingly unrelated diseases seem more similar while their causes are the focus of research.

Alzheimer's disease, diabetes and atherosclerosis all involve the accumulation of apparently deleterious proteins. Inflammation plays a role in all of them. Insulin resistance is found in both type 2 diabetes and Alzheimer's disease. All three diseases become more common with age, and a person with one of these diseases is at increased risk for others.

The idea that germs could cause senile dementia goes back at least to 1907.[1] But the notion of pathogens as an important factor of Alzheimer's disease, type 2 diabetes, cancer, peptic ulcers or atherosclerosis has given way to dementia. other seemingly more convincing theories, until surprising exceptions begin to manifest themselves.

In 1989, Michael Bishop and Harold Varmus were awarded the Nobel Prize for the discovery that some retroviruses could cause cancer. In 2005, Barry Marshall and Robin Warren received the same award for discovering that a bacterium was causing gastritis and peptic ulceration. And in 2008, Harald zur Hausen was informed that the human papillomavirus can cause cervical cancer.

Could a similar event be reserved for Alzheimer's disease, diabetes and atherosclerosis?

The link emerges between viruses and Alzheimer's disease

For Alzheimer's disease in particular, the evidence is enticing. Researchers of this disease have long focused on the formation of amyloid plaques and tau entanglements. Without really knowing why these molecules were created, they focused on their elimination. But experimental treatments do not seem to improve dementia, which is the main symptom of the disease.

"I think the amyloid theory is more or less endangered, amyloid being a byproduct," says Jørgen Rungby, MD, PhD, professor of endocrinology and neuroscience. University of Copenhagen, Denmark, which studies the relationship between Alzheimer's disease and type 2 diabetes.

But a byproduct of what, exactly? Ruth F. Itzhaki, PhD, thinks she knows. Emeritus Professor of Neuroscience and Experimental Psychology at the University of Manchester, UK, Itzhaki noted in 1997 that 60% of people with Alzheimer's disease had both the virus and the disease. Herpes simplex type 1 (HSV1) and the apolipoprotein E gene (APOE). -ε4).[2]

Although the virus is present in the brain of most people over 70, people who have developed Alzheimer's also carry the gene. She and others have postulated that the gene weakens resistance to the virus. The researchers found that gene carriers are also more vulnerable to cold sores and genital ulcers caused by herpes viruses.[3] After an initial infection, the virus can remain dormant until the immune system weakens further with age.

Other researchers found viral DNA in amyloid plaques and tau protein in HSV1-infected cell cultures, which led them to conclude that these proteins constituted a mechanism for defense against the virus.[3] In one study, beta-amyloid reduced the growth of Escherichia coli up to 200 times in vitro, and was also active against Candida albicans.[4]

"First, antimicrobial proteins cause membrane destruction, effectively killing the pathogen," said Lathe. "Then, it is increasingly obvious that the aggregation of these proteins causes agglutination, the microbe is trapped in these insoluble matrices."

Will this open up new treatment possibilities?

If Alzheimer's disease is caused by a virus, then it would be useful to remove it, a theory that relies on new evidence. In Taiwan, where infection data are carefully conserved, researchers found that HSV-infected patients treated with anti-herpes agents were at risk of developing senile dementia, while untreated HSV-infected patients had a risk of senile dementia of 28.3%. (Researchers focused on senile dementia because not all patients had been definitively diagnosed with Alzheimer's disease.)[5]

The discovery is enough to convince Lathe of the clinical implications. "If you have a patient with herpes simplex manifest, do not wait until it disappears, but if you can, intervene with an aggressive antiviral drug," he says. "It's a very good idea because this patient might not contract Alzheimer's disease later."

However, the approach has not been tested in a prospective trial, nor are antivirals as a treatment for patients who have already developed dementia. One possibility is that they prevent the virus from reaching the brain, but can not repair the damage once the virus is there.[3]

Extend the viral link to other conditions

Similar but less spectacular results showed that viral infections were associated with schizophrenia,[6] epilepsy,[3] Parkinson disease,[7] and depression.[8] Lathe is working on the theory that prions are also antimicrobial.

Lathe also thinks that similar mechanisms may explain atherosclerosis, which, like Alzheimer's disease, is associated with vascular occlusion and decreased cerebral blood flow. The same allelic variants in genes, including APOE, increase the risk of contracting these two diseases, as well as hyperlipidemia. In addition, atherosclerotic lesions contain beta-amyloid.[9]

By thoroughly examining the biochemistry of both conditions, Dr. Lathe assumes that the infection leads to inflammation, including the production of 25-hydroxycholesterol to defend against viruses. The resulting cascade ends with "intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion and overt disease".[9]

For type 1 diabetes, theories of infection are less controversial. Although no one knows exactly what triggers the process, most researchers believe that a pathogen triggers an immune response that deteriorates and turns into an autoimmune attack of the pancreas.

Genetic predisposition is essential, but prevalence varies among genetically similar populations and even among identical twins. Sudden cases of type 1 diabetes have been reported in association with mumps, parainfluenza virus, human herpesvirus and enteroviruses, among other pathogens.[10]

"The protein deposited in diabetes, called amylin, is also an antimicrobial protein," says Lathe.

Evidence for Type 2 Diabetes

Could these infections also play a role in type 2 diabetes? The increase in prevalence has so much parallel to the introduction of the Western way of life and the rise of obesity that questions about infection have not gained much of ground. Some researchers believe that infection also plays a role.

For example, they note that periodontitis is a common risk factor for several chronic inflammatory disorders, including atherosclerosis, stroke, diabetes, and Alzheimer's disease.[11]

Infections with Helicobacter pylori and Borrelia are also associated with diabetes. And amyloid beta and amylin deposits, similar to those of Alzheimer's disease, are present in more than 95% of patients with type 2 diabetes. These findings prompted people to think that a common process is developing in these diseases, again involving an immune response in which beta-amyloid and amylin act as antimicrobials but can not completely contain infections or damage them. even healthy tissues.[11]

"If you are an antimicrobial protein produced by a human, you have a hard time being 100% toxic to microbes and 0% to human cells," says Lathe. "There will always be some toxicity."

Remaining questions

Lathe recognizes that many details need to be addressed and that some evidence is contrary. To cite just one example, knock out the APOE Gene delays Alzheimer's disease but accelerates atherosclerosis in a mouse model of this disease.[9]

But perhaps the biggest problem is that no microbe has been definitively proven to cause any of these diseases. Aside from herpes simplex in Alzheimer's disease, researchers have not even found a major suspect. So many experts remain skeptical.

"We know that there is inflammation involved in these diseases," Rungby says. "But it is very unlikely that this inflammation is caused by a virus or bacteria." If that were the case, the pathogens would have already been identified, he argues.

He sees links between diseases, although he does not necessarily tolerate the classification of Alzheimer's as "type 3 diabetes". Both conditions involve insulin resistance and low glucose metabolism, he notes.

Rungby participated in a study on liraglutide, a type 2 diabetes medicine, in Alzheimer's disease. Glucose metabolism has improved in the patients' brains.[12] Although the study is not important enough to detect cognitive effects, a larger trial is underway.

A variety of other diabetes medications have been tried in Alzheimer's disease. Insulin administered intranasally has had promising results.[13]

The exploration of drugs for atherosclerosis for Alzheimer's disease and vice versa has not progressed as far. But tests in mice suggest that acyl-CoA cholesterol acyltransferase inhibitors and acetylcholinesterase inhibitors might work in both cases. The results suggest many possibilities to try treatments for one disease over another.[9]

Do these results relieve us of the injunction to eat better, exercise and sleep better? No luck, said Tour. Antimicrobials found in plants – curcumin and resveratrol are just two of hundreds of possible examples – can attack the microbes responsible for diabetes, atherosclerosis and Alzheimer's disease. So it's always interesting to eat a lot of fruits and vegetables, says Lathe. And exercise strengthens the immune system.

For now, a healthy lifestyle remains the best defense against the biggest killers of the 21st century.

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