Tau Proteins Are Infectious
Neurodegenerative disease is the fastest-growing cause of death in the world. There are more questions than answers surrounding this global epidemic, but researchers are connecting the dots to deadly proteins that are killing many mammals, including humans.
The destructive progression of Alzheimer’s disease follows the growth and spread of toxic protein clumps in the brain.
When doctors perform autopsies to look at the brain tissue of people with Alzheimer’s disease, they find toxic buildups of certain proteins – in particular, a protein called tau – in structures called ‘aggregates’. People with more severe dementia have more tau aggregates in their brain. Aggregates form when individual proteins stick together in repetitive patterns, much like the way a single Lego block might attach to another identical one.
Now, a team of researchers from University of Texas Southwestern Medical Center, University of Delaware and Washington University in St. Louis have identified a single protein “seed” that begins the harmful chain of events in this and other tau protein disorders (tauopathies).
“Alzheimer’s disease (AD) is the most common neurodegenerative disease in. Aggregation of the β-amyloid (Aβ) peptide within the brain is thought to spark the AD pathogenesis. Many recent studies in transgenic mice have proven that Aβ aggregates become self-propagating (infectious) during disease, leading to a cascade of protein aggregation in the brain, which may underlie the progressive nature of AD. The ability to self-propagate and the existence of distinct “strains” reveals that Aβ aggregates exhibit many properties indistinguishable from deadly prions. We have evidence that Aβ can become a prion during disease,” said Prusiner. “I learned that scrapie, Creutzfeldt-Jakob disease and kuru had all been shown to be transmissible by injecting extracts of diseased brains into the brains of healthy animals. Whether prions are responsible for common neurodegenerative diseases, such as Alzheimer’s disease is a possibility that should not be ignored.”
Like all proteins, tau is built from a string of amino acids that folds into a specific shape. Normally folded tau proteins do not form aggregates. It was not clear that an individual tau protein had two distinct forms—structures associated with health (“good”) or disease (“bad”). The research appeared in the open-access journal eLife.
Around 5.7 million Americans live with Alzheimer’s disease (AD), and experts expect the number to rise as the population ages. The disease causes neurodegeneration in part due to the accumulation of tau protein clumps called tangles or aggregates.
Previously, researchers thought tau aggregates would build up where tau proteins were abundant. Like salt crystals grown in a briny solution, they simply needed another tau clump to act as a seed.
Scientists thought these seeds, or templates, themselves comprised large clumps of tau. They also thought such a clump could act as a mobile point of origin, or nidus, for other clumps to build on.
“Somehow, these seeds may actually even move from one cell to another and, when they get into a new cell, they promote new formations in that cell,” said Dr. Marc Diamond, who directs the Center for Alzheimer’s and Neurodegenerative Diseases at University of Texas Southwestern Medical Center.
To test these and other hypotheses, the team set out to find the initial molecular trigger that prompts tau proteins to begin forming toxic clumps.
“What is the first, kind of, molecular event where you’re normal and then something happens, and then you start to develop this disease? And what we’re saying is, you can trace that back to a single protein changing its shape,” said Diamond.
To their surprise, he and his colleagues discovered that a single tau protein could seed an aggregation. That’s because tau proteins exists in two distinct, stable forms: an inert, harmless version and a type that promotes clumping.
What’s more, the harmless shape can change into the damaging one, whose more open structure exposes key amino acids that promote aggregation. Like a wad of one-sided tape uncurled to expose its sticky side, these “bad” tau proteins more readily assemble into toxic aggregates.
The process resembles prions, the infections proteins that cause Creutzfeldt-Jakob disease and mad cow disease. In fact, Diamond’s lab began calling tau proteins prions in 2014, although the prion hypothesis remains controversial.
Identifying how tau proteins go bad could help doctors develop new treatments, earlier diagnostics tests and, someday, perhaps even a vaccine. A better understanding of tau pathologies could contribute to treatments for roughly 25 rarer tau disorders as well.
Tau proteins can convert from an inert shape to a misfolded shape that seeds the growth of fibers that contribute to the pathology of Alzheimer’s disease. Most of the time, proteins fold into a single stable shape to perform their role in the body, but occasionally they can adopt a different conformation. These ‘misfolded’ proteins can be associated with a range of degenerative conditions known as amyloid disorders, which includes the transthyretin amyloidoses as well as Alzheimer’s and Parkinson’s diseases.
Tau forms amyloids that underlie neurodegeneration in a variety of neuropathological syndromes, collectively termed tauopathies. Amyloids are ordered protein assemblies that underlie multiple disorders such as Alzheimer’s disease. Amyloid-forming proteins include tau, synuclein, and expanded polyglutamine proteins such as huntingtin, among many others.
A variety of factors can trigger neurodegenerative disease, including genetics, head trauma and neurotoxins. Deadly, self-replicating tau proteins (prions) appear to be one of those neurotoxins. Unfortunately, these deadly proteins migrate, mutate, multiply and kill with unparallelled efficiency.
Prions (PREE-ons) are a deadly and unstoppable form of protein that migrates, mutates, multiplies and kills with unparalleled efficiency. Dr. Stanley Prusiner, an American neuroscientist from the University of California at San Francisco, coined the term as a contraction of proteinaceous infectious particle. The operative word is “infectious.”
Prions cause fatal neurodegenerative disease in humans and other animals by converting the cellular version of prion protein into a toxic form that erodes the brain and body. Prions migrate, mutate and multiply. They get stronger as they move up the food chain. At the top of the food chain, humans are highly vulnerable to prion disease. The prions shed from humans are the deadliest and most aggressive. Mismanaging human prions is a big mistake.
Dr. Prusiner earned a Nobel Prize in 1997 for discovering and characterizing prions and prion disease. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the importance of his research. Unfortunately, Prusiner’s science is being ignored and we all are facing a public health disaster because of the negligence and reckless disregard for public health.
Prions are a formidable threat to public health. When the U.S. government enacted the Bioterrorism Preparedness and Response Act of 2002, it included a provision to halt research on infectious prions in all but two laboratories. It classified prions as select agents that pose an extreme risk to food, water and health systems. Unfortunately, the Center For Disease Control quietly took prions off the list about two years ago because the classification criminalized multi-billion dollar industries and many industry practices.
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Gary Chandler is a prion expert. He is the CEO of Crossbow Communications, author of several books and producer of documentaries about health and environmental issues around the world. Chandler is connecting the dots to the global surge in neurodegenerative disease, including Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and other forms of prion disease. The scientific name for prion disease is transmissible spongiform encephalopathy. The operative word is “transmissible.” Even the global surge in autism appears to be related.