Can Alzheimer’s disease be caused by an infection? | | Alzheimer’s disease

aDavangele Devanand, a neurologist at Columbia University Medical Center, was combing through a ton of scientific data on Alzheimer’s when he came across a startling idea.

“I was looking for a therapeutic approach for Alzheimer’s disease that would have a reasonable effect,” he says. “I discovered this old theory linking the herpes virus to disease 35 years ago. I had indirect evidence for all of this.”

The more Devanand looked, the more he discovered. Since the mid-80s, a handful of scientists around the world have believed that either viruses or bacteria cause Alzheimer’s disease, despite near-total backlash from those studying the more accepted theory of Alzheimer’s disease. I have enthusiastically pursued the idea that it might be involved in disease. Colleagues belittled them, major scientific journals and conferences rejected their work, funding was bare, but slowly but surely they built an increasingly compelling case.

In particular, there was evidence pointing to herpes simplex virus 1 (HSV-1). 70% of the UK populationand causes of herpes labialis – as prominent suspects. England, France and scandinavia It suggests that people infected with herpes are more likely to develop Alzheimer’s disease. Professor Ruth Yitzhaki of the University of Oxford Institute of Population Aging, who has done more to advance his HSV-1 theory of Alzheimer’s disease than any other scientist, said: examined postmortem brain samples She found more viral DNA in patients than in people who hadn’t died from the disease.

“Then there was This 2018 study It was very dramatic,” says Devanand. “Treatment of a herpes patient with standard antiviral drugs reduced his risk of dementia by a factor of nine.”

Devanand was intrigued because, although the key features of Alzheimer’s disease are well known, we still know very little about what causes it. Certain genetic and lifestyle factors, such as loneliness, lack of exercise, and an unbalanced diet, can all increase the risk of developing Alzheimer’s disease. But how and why it starts remains a mystery. Could viruses be the definitive weapon scientists have been looking for?

others have suggested that various bacteria It can also cause neurodegeneration leading to Alzheimer’s disease. Chlamydia pneumoniae, cause lung disease, Borrelia burgdorferi, It’s been linked to Lyme disease, and it’s been proposed that everything, even gum infections, can be a trigger.

The main idea of ​​why viruses like HSV-1 and possibly bacteria can cause Alzheimer’s disease is that the virus enters the central nervous system and enters the body before reaching the brain in middle age. That’s it. Once there, they reactivate in old age because the aging immune system can no longer control them, or something else (a traumatic episode, head injury, or perhaps another infection) brings them back to life. They remain dormant for years until they do.. Upon awakening, theory suggests, they start wreaking havoc.

Neurologists long dismissed these ideas as fantastic until more and more irrefutable evidence emerged for the role of pathogens in chronic disease. Identified as a major risk factor In the case of multiple sclerosis, other studies have shown that bouts of measles can lead years later to a progressive neurological disorder called subacute sclerosing panencephalitis.

When Devanand approached the National Institute on Aging, millions of dollars in grants They agreed to endorse him to conduct a clinical trial investigating whether a herpes antiviral drug called valacyclovir could slow the progression of Alzheimer’s disease in patients in the early stages.

The ongoing trials, which are expected to be completed by early 2024, could have a significant impact on how we view the disease.

---

debtFor decades, the primary focus of nearly all Alzheimer’s disease efforts has been a protein fragment called beta-amyloid, often simply called amyloid. Funding groups and drug developers have largely avoided alternative explanations for why Alzheimer’s disease occurs, suggesting an alternative. has continued to devote resources to amyloid research.

But scientists are beginning to show that the amyloid and microbial theories in Alzheimer’s disease may not be mutually exclusive. Scientists in the department believe that amyloid is actually a key component of the brain’s defense mechanisms against external threats. Rudolf Tanzi, Professor of Neurology at surprising discovery – Amyloid has antibacterial properties and helps protect the brain from invading pathogens. After more than a decade of experimentation, he developed a workable theory as to why plaques form.

“When an infection hits the brain, the first response is these little sticky peptides that bind to the microbe, glutinate it and trap it in a ball,” he says. I believe that the plaques found in the Alzheimer’s brain actually evolved as a way to protect the brain.”

According to Tanzi, for most of our lives, our bodies are able to seamlessly clear these amyloid clumps. Immune cells known as microglia cleanse the brain of debris and devour them during deep sleep. But as we age, this finely tuned system can break down, and if amyloid remains in the brain, it will eventually harm us.

People with certain genetic vulnerabilities, such as the APOE4 gene variant up to 25% of the general population – Amyloid is more likely to accumulate because it cannot be shoveled out as efficiently as others.Aging also weakens the immune system, making the brain more accessible to pathogens. , forming more amyloid.

“As we age, our immune system begins to wane, and the barrier between blood flow and the brain isn’t what it used to be,” says Tanji. “So the microbes are able to grow better, and the brain doesn’t clear as much amyloid as it used to, creating a perfect storm.”

Hugo Reebheim, a geriatrics researcher at Umeå University, says he also knows that lifestyle factors such as social isolation and lack of exercise can weaken the immune system. suggests that it may have two consequences. That means it’s harder for the body to keep her HSV-1 and other microbes in check, and as a result, she can’t clear the plaque.

“We know that psychological factors and stress can influence the risk of losing control of a herpes virus infection at a given point in time,” said Lövheim.

---

T.The burden of Alzheimer’s disease and all forms of dementia on patients, families and society as a whole is indescribable. by next year over 1 million In the UK with dementia, numbers our healthcare system can’t handle.The total cost of dementia care in this country is about £34.7 billion 1 year, but the toughest stat is that two-thirds Part of this burden is covered by the families themselves, either through unpaid care or private social care.

However, the Alzheimer’s disease treatment landscape is not sparse. Almost all clinical trials testing drugs that try to reduce the amount of amyloid in the brain have failed to stop the disease. hit the headline Towards the end of 2022, it offers little benefit in delaying amnesia.His Derek Lowe, a medicinal chemist who blogs about the pharmaceutical industry for the journal chemistrylecanemab shows that while amyloid is definitely involved in Alzheimer’s disease, it is unlikely to be the underlying cause.

“Lecanemab does indeed show substantial amyloid clearance in the brain, so it is definitely working on its target.” Rowe wrote. “The fact that this drug has such an effect on amyloid and yet hardly slows the course of the disease supports that point of view.”

Some scientists believe that anti-amyloid drugs have been ineffective in preventing Alzheimer’s disease because the disease progresses too slowly, years or decades after plaque begins to build up. At this point, it’s the widespread neuroinflammation that’s killing the cells, and why some companies, such as Switzerland-based AC Immune, are now trying to target inflammatory pathways in the Alzheimer’s brain. That’s why.

Anti-amyloid drugs could be tried in middle-aged people to see if they stop the disease from developing, but the cost is likely to be impractical, Tanzi said. “If every American had an amyloid blood test today, 40 million people would realize they needed to do something about it,” he says. “But if you’re taking anti-amyloid treatments that cost $26,000 a year, we’d love to be able to get them to 40 million people, especially to make sure they don’t have swelling or bleeding in their brains, each of them three times a year. Especially when it requires multiple MRI scans.It’s a side effect.”

Instead, if scientists can produce more evidence that microbes reliably cause disease in at least some patients, it could open the door to more practical disease prevention initiatives. It could be possible to make antiviral drugs available to all people infected with , or to promote vaccination in middle age, such as the varicella-zoster virus (VZV) that causes shingles. VZV has been suggested to be able to reactivate her HSV-1 virus from dormancy, and Itzhaki i found that The shingles vaccine appears to reduce the risk of developing Alzheimer’s disease.

But Alzheimer’s is a very complex disease, and much work remains to be done to convince the majority of scientists that an infectious disease is involved. Canadian scientists gave Alzheimer’s patients multiple antibiotics, but nothing worked. San Francisco-based biotech Cortexyme – now known as Quince Therapeutics – is Porphyromonas gingivalisa bacterium that causes periodontal disease and secretes harmful enzymes that can leak into the brain.

Tanzi suspects it’s too late to treat the patient. “If an infection has driven amyloid formation, it could have happened 30 years ago,” he says. “It took me 30 years to develop enough neuroinflammation to get sick.”

Devanand’s trial would provide conclusive evidence as to where to go next. Providing antiviral drugs to people in their 40s and 50s who are genetically at risk for Alzheimer’s disease, or vaccinating large numbers of people against a variety of common viruses, if there is any indication of benefit. may help persuade funding bodies to

Devanand and scientists like Itzhaki, who have devoted their lives to this line of research, are hoping for hints that they are on the right track. “This test does not cure disease,” he says. “We’re looking at whether patients who receive antivirals experience less decline than those who receive a placebo. And if herpes is a contributing factor, it’s good to treat it.” That’s it.”