Prions Detected in Eyes of Patients With Brain Disease

Creutzfeldt-Jakob disease (CJD) is a fatal brain disorder that destroys brain cells, causing tiny holes in the brain. Symptoms of CJD are ataxia, or difficulty controlling body movements, abnormal gait and speech, and dementia. The disease is always fatal and has no cure.¹

CJD is one of several transmissible spongiform encephalopathies (TSEs). These are a family of progressive neurodegenerative disorders affecting animals and humans. Bovine spongiform encephalopathy (BSE), also known as mad cow disease, presents in much the same way as CJD.

The U.S. Food and Drug Administration (FDA) issued a regulation in 2009 banning specific proteins in feed to prevent the spread of BSE.² However, the regulation superficially addresses the issue. For instance, slaughterhouse waste products continue to be recycled into bone and blood meal as additives to livestock and pet foods.³

This increases the risk of livestock acquiring BSE as it has proven to be a foodborne-derived disease,^4,5 and eating beef from cows with BSE triggers a variant of CJD.⁶

CJD is difficult to diagnose, as taking a brain biopsy to rule out a disease is impractical. The National Institutes of Health have recently published work from colleagues at the University of California San Diego and San Francisco who have measured the distribution and levels of prions in the eye.⁷

Prions in the Eyes May Indicate Brain Disease

Prions are abnormal forms of proteins collecting in brain tissue and causing cells to die. This leaves sponge-like holes in the brain. BSE and CJD are the result of a prion infection that is untreatable and always fatal.

Byron Caughey, Ph.D., from the National Institute of Allergy and Infectious Diseases, collaborated with researchers from Nagasaki University and developed a method to test brain and spinal cord fluid for the presence of prions in an effort to improve diagnosis of CJD in a clinical setting.⁸

Dr. Christina J. Sigurdson, professor of pathology at UC San Diego and Davis was on the team, and commented on the problems associated with sporadic CJD (sCJD), a form appearing without known risk factors and accounting for nearly 85 percent of diagnosed cases:^9,10

"Almost half of sCJD patients develop visual disturbances, and we know that the disease can be unknowingly transmitted through corneal graft transplantation. But distribution and levels of prions in the eye were unknown.

We've answered some of these questions. Our findings have implications for both estimating the risk of sCJD transmission and for development of diagnostic tests for prion diseases before symptoms become apparent."

The technique, called real-time quaking-induced conversion (RT-QuIC) is currently in use. More recently, Caughey and colleagues attempted to use the same technique to measure the distribution and level of prions in the eye. They recruited 11 people with known CJD and six with other types of fatal diseases to serve as controls. All agreed to donate their eyes for post-mortem analysis.

The researchers found evidence of prions throughout the eyes of the 11 people with CJD but not in the six control patients. This discovery suggests eye tissue may be another avenue for early diagnosis of CJD and raises the question of whether prions may be transmitted through a clinical eye procedure if the instruments or transplanted tissues have been contaminated. Caughey comments:¹¹

"By testing various components of the eye with the RT-QuIC assay, we found that prions can collect throughout the eye — including the fluid inside the eye.

Our findings suggest that we may be able to develop methods of detecting prions in eye components even before symptoms develop, which may help prevent unwitting transmission of prions to others through contaminated medical instruments or through donor tissue."

Prion Diseases Are Transmissible Between Animals and Humans

Some prion diseases are transmissible between humans and animals. Chronic wasting disease (CWD) is a form of BSE affecting deer, elk and moose. Infected animals may take up to one year to develop symptoms including drastic weight-loss, stumbling and other neurological symptoms, often dying within three years.

The Quality Deer Management Association¹² mapped out the number of hunters who killed whitetail deer in four Wisconsin counties with the highest incidence of CWD in the state. The organization believes hunters from 49 states killed deer in this Wisconsin CWD hotbed in the 2016-2017 deer season.

Of the 32,000 deer killed, 22,291 were tested, finding 17 percent positive. By extrapolating data, the researchers estimate approximately 5,000 of those untested were also positive.

Most deer with CWD appear healthy. Hunters transporting carcasses across state lines were breaking regulations in many states now banning the importation of specific animal parts to prevent CWD from entering their state.

The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend testing all deer carcasses and waiting for the all-clear before you eat the venison. If the deer tests positive, it should be safely discarded.¹³

Previous research¹⁴ noted a close similarity between human and rodent prion proteins shown to be protease resistant and infective. The researchers hypothesized that since rats and mice are known to be susceptible to prion diseases, ingestion of infected parts, potentially droppings, could be a mode of transmission of BSE to humans, resulting in CJD.

Eating beef infected with mad cow — which, again, is very similar to CWD — is known to cause CJD in humans. Symptoms are similar to Alzheimer's and include staggering, memory loss, impaired vision, dementia and, ultimately, death. Between 2002 and 2015, the prevalence of CJD rose by 85 percent across the U.S. In 2015, there were 481 cases.¹⁵

The first case of CWD was recently diagnosed in reindeer in Norway, which researchers theorized may have occurred when bottled North American deer urine was transported for use as a lure. In an effort to eradicate the disease before it spread, an advisory panel for the Norwegian Scientific Committee for Food Safety recommended the entire herd be culled.¹⁶

Alzheimer’s Disease Is on a Spectrum of Transmissible Prion Diseases

The age at which Alzheimer's may be diagnosed has been falling. Where in past decades it was found almost exclusively in those over 65, today it may be diagnosed in people as young as 51.¹⁷

The spectrum of transmissible spongiform encephalopathies include Alzheimer's disease, Parkinson's and CJD. Since prions can be found in urine, feces, blood and other bodily fluids, the spread of these fluids may contribute to the spread of other prion disease mutations.

Alzheimer's disease is officially the sixth leading cause of death in the U.S., although more recent data suggests it may be the third leading cause of death, right after heart disease and cancer.

As deaths from heart disease have declined nearly 11 percent from 2000 to 2015, deaths from Alzheimer's have increased 123 percent.¹⁸ Nearly 33 percent of seniors will die with some form of dementia, killing more than breast cancer and prostate cancer combined.

The financial burden reaches $232 billion. According to the Alzheimer's Association¹⁹ an estimated 5.7 million Americans of all ages have Alzheimer’s dementia, including nearly 200,000 under the age of 65.

These growing statistics may be related to both lifestyle factors and a potential infectious component. In one study,²⁰ researchers found when mice were injected with tissue from a human who had Alzheimer's, the mouse began to exhibit changes characteristic of the disease.²¹

Dr. Claudio Soto, professor of neurology at the University of Texas Medical School theorized these findings open the possibility some sporadic cases may arise from an infectious process.²²

Sotto warned that even if the data was corroborated it would still be important to avoid well-known risk factors for Alzheimer's, since these may accelerate the disease or increase the risk in cases where there is an infectious origin.²³

Autopsies Reveal a Potential Infectious Process

Subsequent research published in Nature²⁴ showed data from autopsy studies where individuals who had died from CJD appeared to have contracted the disease decades earlier from contaminated growth hormone extracted from human cadavers. In addition, six also harbored amyloid pathology associated with Alzheimer's disease.

Molecular neuroscientist John Hardy of the University College London believed this was the first evidence of real-world transmission of amyloid pathology and that it is particularly concerning. The researchers also determined none of the individuals carried genetic material predisposing them to early onset Alzheimer's or any other neurodegenerative diseases.

They believe the most plausible explanation for the amyloid pathology was it had been transmitted by human growth hormone extracts contaminated with beta amyloid seeds as well as the CJD prions.

In another study,²⁵ researchers performed autopsies on individuals who died of CJD, all of whom received surgical grafts of dura mater prepared from human cadavers contaminated with the prion protein known to cause CJD.

However, in addition to the damage from CJD, five of the seven brains displayed pathological signs associated with Alzheimer's disease, including plaques formed from beta amyloid protein. These individuals were 28 to 63 years old and considered unusually young to have these changes.

Data was compared against a set of 21 controls who had not received surgical grafts but died of sporadic CJD. They did not have the amyloid signature. The results of both studies are consistent, demonstrating the same pathology emerging after different medical procedures.²⁶ 

The scientists emphasized neither study demonstrates the disease is transmitted through normal contact, and they stress cadaver derived preparations are no longer used. This does have important clinical implications for the sterilization of surgical instruments, however, since beta amyloid proteins are very sticky and may not routinely be removed during standard sterilization procedures.

Eating Habits Increase Risk of Alzheimer’s Disease

Unfortunately, misinformation and mismanagement may be contributing to a rising number of deaths from neurodegenerative diseases, which experts suggest may triple by 2050.²⁷ While these numbers are large, they may not be accurate.

The Alzheimer's Association believes physicians in the U.S. only inform 45 percent about their diagnosis and this suppression of information is most likely at work in other countries as well.²⁸ Lifestyle factors are also implicated in the development of Alzheimer's disease.

One of the most striking studies²⁹ on carbohydrates and brain health revealed a high-carbohydrate diet increased the risk of dementia by 89 percent, while high-fat diets lowered it by 44 percent.

Other studies have also strongly suggested Alzheimer's dementia is connected to insulin resistance³⁰ and even mild elevations may be associated with an elevated risk of dementia.³¹ Diabetes and heart disease are known to elevate your risk, both of which are rooted in insulin resistance.

This interconnection between high-sugar diets and Alzheimer's was again highlighted in a longitudinal study³² in which over 5,000 individuals participated. Over a decade’s worth of data revealed the higher an individual's blood sugar was, the faster the rate of cognitive decline.

Increased blood sugar from consuming sugar and other carbohydrates can disrupt your brain function even when you're not diabetic or have other signs of dementia.

Using short- and long-term glucose markers, one study³³ evaluated healthy, nondiabetic, nondemented seniors. Memory tests and brain imaging revealed the higher the blood glucose measured, the greater the compromise in memory and structure of the hippocampus. In yet another study,³⁴ researchers found Type 2 diabetics lost more gray matter with age than expected, and had earlier onset of dementia than nondiabetics.

Lack of Sleep and Activity Also Increase Your Risk of Dementia

A lack of sleep has also been linked with beta-amyloid buildup found in Alzheimer's disease. Deep sleep is particularly important, as it is only during deep sleep that your brain’s glymphatic system is activated, allowing it to flush away cellular waste.³⁵

Persistent patterns of poor sleep may actually be an early indicator of amyloid buildup causing a subtle brain change well before the disease develops. Guidelines suggest most adults need seven to nine hours of sleep each night and children and teens need even more.

Long periods of sitting also impact memory in middle-aged and older adults. Research data³⁶ using high-resolution magnetic resonance imaging (MRI) on a group of 35 middle-aged and older adults found brain thinning in a region involved in the formation of new memory.

In addition to the MRIs, the participants assessed their physical activity level and average number of hours spent sitting. Comparing this data, the researchers found sitting for extended periods of time was closely associated with thinning in the medial temporal lobe of the brain.

Preventive Strategies

It is often believed dementia is a condition that can't be controlled, but there are many factors you can influence to greatly reduce your risk. It is important to address several factors and not focus on only one or two.

That said, improving your cardiovascular fitness is an excellent place to start, as I discuss in my previous article, "How to Decrease Your Risk for Dementia by 90 Percent." When combined with other approaches to resolve mitochondrial dysfunction, it can be highly effective in preventing cognitive decline.

Other strategies to help you reduce your risk of Alzheimer’s disease include eating a ketogenic diet, optimizing your vitamin D and omega-3 levels, eliminating gluten and processed foods, and intermittent fasting. See the lifestyle strategies I believe to be most helpful and important to reduce your risk of Alzheimer’s disease in my previous article, "Link Between Sugar and Alzheimer's Strengthens."

To learn more about Alzheimer’s and the tests that can help diagnose it early, see my interview with Dr. Dale Bredesen, author of "The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline."

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