“Are Prions behind All Neurodegenerative Diseases?” WOW! The answer seems to be YES!

Prions are known to cause Creutzfeldt-Jakob disease (the human version of mad cow disease) and kuru (in Papua, New Guinea), and have been implicated in Alzheimer’s disease, Parkinson’s disease, Huntinton’s disease, and amyotrophic lateral sclerosis (ALS).

What if prions were also responsible for mental illness? Those are a kind of neurodegenerative disorder as well!!


Evidence mounts that chain reactions involving toxic proteins link Creutzfeldt–Jakob disease, Alzheimer’s, Parkinson’s and more

brain with Alzheimer's disease
Alzheimer’s disease (bottom) destroys neurons in many areas of the brain, including those responsible for memory.

In the human form of mad cow disease, called Creutzfeldt-Jakob, a person’s brain deteriorates—literally developing holes that cause rapidly progressing dementia. The condition is fatal within one year in 90 percent of cases. The culprits behind the disease are prions—misfolded proteins that can induce normal proteins around them to also misfold and accumulate. Scientists have known that these self-propagating, pathological proteins cause some rare brain disorders, such as kuru in Papua New Guinea. But growing evidence suggests that prions are at play in many, if not all, neurodegenerative disorders, including Alzheimer’s, Huntington’s and Parkinson’s, also marked by aggregations of malformed proteins.

Until recently, there was no evidence that the abnormal proteins found in people who suffer from these well-known diseases could be transmitted directly from person to person. The tenor of that discussion suddenly changed this September when newly published research in the journalNature provided the first hint such human-to-human transmission may be possible. (Scientific American is part of Springer Nature.)

For the study, John Collinge, a neurologist at University College London, and his colleagues conducted autopsies on eight patients who died between the ages of 36 and 51 from Creutzfeldt-Jakob. All the subjects had acquired the disease after treatment with growth hormone later found to be contaminated with prions. The surprise came when the researchers discovered that six of the brains also bore telltale signs of Alzheimer’s—in the form of clumps of beta-amyloid proteins, diagnostic for the disease—even though the patients should have been too young to exhibit such symptoms.

These observations suggest that the tainted hormone injections might have carried small amounts of beta-amyloid proteins that triggered the formation of more such proteins. Neither Alzheimer’s nor any known human prion diseases are contagious through direct contact. Yet human transmission of prion diseases has occurred through certain medical procedures and, in the case of kuru, cannibalism. The new study therefore raises the possibility that Alzheimer’s is a transmissible disease with an etiology akin to prion diseases.

The new finding is provocative, but experts advise caution in interpreting the results. For instance, neuroscientist John Trojanowski of the University of Pennsylvania points to the small size of the study and lack of direct evidence for transmission in support of causality. But if it is eventually shown that Alzheimer’s and other neurodegenerative diseases indeed share the same basic pathological pathway and mechanism, treatments could target one and all.

“Transmission may occur in only a small percentage of human cases,” says Claudio Soto, a professor of neurology at the University of Texas Health Science Center at Houston. “But the underlying principle is the most important thing that could lead to new opportunities for therapeutic interventions and diagnostics.” Investigators such as Soto and Collinge are working on ways to detect in body fluids the presence of small clumps of the transmissible proteins now thought to be involved in Alzheimer’s and other neurodegenerative diseases, which could represent a diagnostic advance.

Such detection will likely be difficult. A study published online in September in the journal Nature Neuroscience by Mathias Jucker of the University of Tübingen in Germany and his colleagues required extremely sensitive methods to find minuscule clumps of beta-amyloid proteins, referred to as seeds, in mice brains. These seeds appear to be able to regain pathological properties even after six months of lying dormant. These possibly prionlike proteins might therefore exist in the brain long before symptoms develop, at levels too low to be found by routine tests.

One potentially prionlike protein may cause several diseases, according to a study published this summer by Nobel laureate Stanley Prusiner, who discovered prions in the 1980s. Prusiner and his colleagues found that a “strain” of alpha-synuclein—the misfolded protein involved in Parkinson’s—can cause a similar but rare neurodegenerative disease, called multiple-system atrophy. Understanding how variants of these disease-causing proteins differ in shape and how the particular configuration influences their pathogenic nature is destined to become a focus of future research. “There’s evidence that both prions and beta-amyloid exist as different strains and have very different biological effects,” says Lary C. Walker of Emory University, who was involved in the Nature Neuroscience study. “I think understanding this will give us insight into what’s happening in disease.”

As the evidence increases, more scientists now suspect that prionlike processes probably underlie all neurodegenerative disorders. Prusiner expected the current change in thinking: in his 1997 Nobel Prize lecture, he predicted that the understanding of prion formation could “open new approaches to deciphering the causes of and to developing effective therapies for the more common neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).”

And another one: Gut microbiota are related to Parkinson’s disease and clinical phenotype (!!!!)

The human digestive tract contains up to a thousand different types of bacteria, which help you digest  food, make vitamins and maintain your immune system. The amount of bacteria is influenced by diet, age and other variables, and is thus unique to each individual.

Filip Scheperjans, MD, PhD, and colleagues from the University of Helsinki, Finland examined the intestinal contents of 72 people with Parkinson’s and 72 without PD. Their research, funded by MJFF and published recently in Movement Disorders, revealed that people with Parkinson’s had lower levels of a certain bacterium and that concentrations of another bacterium varied among subgroups of those with PD with differing motor symptoms.

Intestines as a Window to the Brain
There is a clear effect of Parkinson’s disease on the gastrointestinal system. Nearly 80 percent of people with PD have constipation, and this condition often predates the motor symptoms of Parkinson’s by several years.

Additionally, alpha-synuclein — a protein that clumps in the brains of all people with Parkinson’s — has been found in several locations outside the brain, including the nerves controlling the intestines. Investigators question whether the abnormal protein could show up here first, causing non-motor symptoms, and later spread to the brain to cause motor symptoms.

Lastly, researchers believe the normal bacteria of the gut might affect the functioning of the gut nerves which could in turn affect the nerves of the brain.

Specific Bacterial Levels Are Affected in Parkinson’s Disease
In Dr. Scheperjans’ study, the bacteria Prevotella was present at lower levels in the guts of people with Parkinson’s disease. This bacterium aids in the creation of the vitamins thiamine and folate and the maintenance of an intestinal barrier protecting against environmental toxins. This finding may therefore have implications not only for diagnosis but also for dietary adjustments or vitamin supplementation for management of PD in the future.

In people with Parkinson’s with more severe postural instability and gait difficulty, as opposed to tremor, the bacterium Enterobacteria was present at higher levels. The reasons for this association were not clear.

Studying Intestinal Bacteria Will Advance Understanding of Parkinson’s
Deciphering information from the gut could lead to earlier and more definitive diagnosis, a better understanding of how Parkinson’s progresses, and ways to separate the populations of people with differing symptoms of PD.

If researchers determine that there are specific and consistent differences in the gut, bacteria may serve as biomarkers — objective measurements to diagnose or track PD. As the gut is much more accessible than the brain and can be analyzed through stool samples, a bacterial biomarker is an attractive prospect.

Additionally, we don’t know why people with Parkinson’s disease show such varied motor symptoms (gait problems versus tremor, for example) or who will get which. Bacterial differences may allow us to separate the subtypes of Parkinson’s and, as a result, give individuals a better idea of the symptoms and disease progression they might expect.

More Research Is Needed
Further studies are called for to learn more about the relationship between these and other gut bacteria and Parkinson’s. In the meantime, researchers are intensely studying alpha-synuclein to determine how and why this protein contributes to Parkinson’s, and its connection between the gut and the brain.

Until a disease-modifying therapy is found, symptomatic treatments, including a drug for constipation, remain under development.

1) https://www.michaeljfox.org/foundation/news-detail.php?gut-check-on-parkinson-new-findings-on-bacteria-levels&utm_source=social&utm_medium=facebook&utm_content=researchnews&utm_campaign=gut-check&s_src=gut-check&s_subsrc=facebook&utm_source=social&utm_medium=facebook&utm_content=foundationnews&utm_campaign=archives-gut-bacteria&s_src=MJFFfb&s_subsrc=archives-gut-bacteria#prclt-aCp1CEDa

In the course of Parkinson’s disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1–V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker. © 2014 International Parkinson and Movement Disorder Society

2) http://onlinelibrary.wiley.com/doi/10.1002/mds.26069/abstract

Noninvasive brain stimulator may ease parkinson’s symptoms in a patient’s homeParkinson’s disease

Master’s students have developed a new portable device to inhibit neuronal firing in critical regions of the brains of people with Parkinson’s disease to stop the tremors associated with that disease. This device is a helmet, which the patient can control, it sends electrical stimulation to the patient’s brain, however the level and duration of the stimulation is controlled by a physician.

The wonderful part about this is that it is portable and under the patient’s control. My father in law had Parkinson’s disease, he was a solid, strong, silent man, and this disease brought him down like tissue paper fluttering from the sky. I’m sure at least some of his symptoms and problems would have been alleviated by this portable helmet!

Article and reference below.


Parkinson’s disease patients whose symptoms such as tremor, muscle stiffness and slowed movement make it tough to hold an eating utensil steady have few options for relief outside of a hospital or clinic. Medication can help, but over time it tends to become less effective. To give these patients another in-home option, Johns Hopkins graduate students have invented a headband-shaped device to deliver noninvasive brain stimulation to help tamp down the symptoms.

The students’ prototype, developed during a yearlong biomedical engineering master’s degree program, has not yet been tested on humans, but it is viewed as a promising first step toward helping Parkinson’s patients safely relieve their own symptoms at home or elsewhere without going to a hospital or doctor’s office. The design has already received recognition at several prominent competitions. On June 9, it won the $5,000 second-place prize in VentureWell’s BMEidea national design contest for biomedical and bioengineering students. In May, the invention earned first-place honors in the People’s Choice Award competition at Johns Hopkins’ Biomedical Engineering Design Day 2015. Earlier, it was a finalist in the Rice University Business Plan Competition.

The five student team members were inspired to build the new device last summer after observing neurosurgery being performed on Parkinson’s patients at Johns Hopkins Hospital. Parkinson’s is an incurable neurodegenerative disorder that affects 1 million people in the United States and 7 million worldwide.

Tremtex team members
From left, the Tremtex team members are Ian Graham, Melody Tan, Erin Reisfeld, Shruthi Rajan and David Blumenstyk. Credit: Will Kirk, Johns Hopkins University

For patients in advanced stages, one treatment option is deep brain stimulation. In this procedure, a surgeon implants thin electrical leads into the region of the brain that controls movement. The leads are connected to a pulse generator—similar to a pacemaker for the heart—that is placed under the skin below the collarbone. This implant sends electrical signals to the brain to help curb some symptoms caused by Parkinson’s.

“We saw that this procedure is really invasive and can take 10 to 15 hours to complete,” said Shruthi Rajan, a team member from Charlotte, North Carolina. “It’s also very expensive, and not all patients qualify for the surgery. We asked if there was a way to provide the same treatment in a less invasive way that doesn’t require brain surgery.”

The students were referred to Yousef Salimpour, a Johns Hopkins Medicine postdoctoral research associate who has been studying a noninvasive Parkinson’s therapy called transcranial direct current stimulation. In this painless treatment, low-level current is passed through two electrodes placed over the head to tweak the electrical activity in specific areas of the brain. The technique can be used to excite or inhibit these nerve cells. The treatment is still considered experimental, but it has attracted much attention because it does not require surgery and is inexpensive, safe and relatively easy to administer without any side effects.

The biomedical engineering students met with Salimpour to learn about the research he conducts in a clinical setting. “We told him we had an idea for a portable home version of this equipment,” Rajan said. “But we planned to add safety measures to make sure the patient used it properly without a doctor or nurse being present.”

The students aimed for a prototype that would enable a patient to activate the battery-powered treatment by touching a large easy-to-press button. With patient safety in mind, the students designed their prototype to deliver current for only 20 minutes daily and only at a doctor-prescribed level.

To help fine-tune their design, the students met with dozens of Parkinson’s patients over a four-month period. Although the students did not administer the actual brain treatment, the patients help them craft the critical headband component so that it would be easy to put on, comfortable to wear and positioned so that the electrodes would remain stable and properly target the motor cortices areas of the brain.

“For a comfortable fit, we put an elastic band in the back and told the patients to put it on like a baseball cap,” said team member Ian Graham, from Old Saybrook, Conn. “The interaction with the patients was really helpful. In our usual college classes, we’re just given a textbook problem to solve. In this program, being able to find a real-life biomedical problem and figure out how to address it was huge. And we even received letters of encouragement from some of the patients we met.”

The other members of the student design team were David Blumenstyk, Erin Reisfeld and Melody Tan.

In addition to the assistance from neuroengineer Salimpour, the student inventors received guidance from other members of an interdisciplinary team of Johns Hopkins medical researchers that includes neurologist Zoltan Mari, neurosurgeon William Anderson and neuroscientist Reza Shadmehr.

“Our group is working on the idea of using noninvasive brain stimulation for Parkinson’s disease symptom control as a new clinical treatment,” Salimpour said. “Our preliminary results were promising. Patients keep asking us for more of this treatment. But we couldn’t provide the treatment for them because there is no portable and FDA-approved device like this for Parkinson’s patients that is on the market at this time. The biomedical engineering students then approached us with the idea of designing the home-based treatment device. They did a great job, and made a fascinating prototype. We hope that based on their preliminary work, Parkinson’s patients will receive the benefit of this new technique at home very soon.”

With help from the Johns Hopkins Technology Ventures staff, the student inventors obtained provisional patents covering the design of the device, dubbed the STIMband. Another Johns Hopkins student team is slated to take over the project in September to further enhance the design and move it closer to patient availability. One addition may be a wireless connection to allow a doctor to adjust a home patient’s treatment level from a remote location.

– See more at: http://www.neuroscientistnews.com/clinical-updates/noninvasive-brain-stimulator-may-ease-parkinson-s-symptoms-patient-s-home#sthash.1LZh448E.dpuf