Wednesday, September 2, 2020

New hope for Alzheimer's disease, spinal cord injury, more


August 27, 2020


DZNE - German Center for Neurodegenerative Diseases


Researchers have developed a neurologically acting protein and tested it in laboratory studies. In mice, the experimental compound ameliorated symptoms of certain neurological injuries and diseases, while on the microscopic level it was able to establish and repair connections between neurons. This proof-of-principle study suggests that biologics, which act on neuronal connectivity, could be of clinical use in the long term.



Researchers from the German Center for Neurodegenerative Diseases (DZNE), UK and Japan have developed a neurologically acting protein and tested it in laboratory studies. In mice, the experimental compound ameliorated symptoms of certain neurological injuries and diseases, while on the microscopic level it was able to establish and repair connections between neurons. This proof-of-principle study suggests that biologics, which act on neuronal connectivity, could be of clinical use in the long term. The results are published in the journal Science.

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The human brain's neuronal network undergoes life-long changes in order to be able to assimilate information and store it in a suitable manner. This applies in particular to the generation and recalling of memories. So-called synapses play a central role in the brain's ability to adapt. They are junctions through which nerve signals are passed from one cell to the next. A number of specific molecules -- known as "synaptic organizing proteins" -- make sure that synapses are formed and reconfigured whenever necessary.

An artificial protein

An international team of researchers has now combined various structural elements of such naturally occurring molecules into an artificial protein called CPTX and tested its effect in different disease models. To this end, the compound was administered to mice with neurological deficits that occur in similar fashion in humans. Specifically, the tests focused on Alzheimer's disease, spinal cord injury and cerebellar ataxia -- a disease that is characterized primarily by a failure of muscle coordination. All these conditions are associated with damage to the synapses or their loss. The study was a collaborative effort by experts from several research institutions, including the DZNE's Magdeburg site, MRC Laboratory of Molecular Biology in UK, Keio University School of Medicine in Tokyo, and, also in Japan, Aichi Medical University.

Easing symptoms of disease

"In our lab we studied the effect of CPTX on mice that exhibited certain symptoms of Alzheimer's disease," said Prof. Alexander Dityatev, a senior researcher at the DZNE, who has been investigating synaptic proteins for many years. "We found that application of CPTX improved the mice's memory performance." The researchers also observed normalization of several important neuronal parameters that are compromised in Alzheimer's disease, as well as in the studied animal model. Namely, CPTX increased the ability of synapses to change, which is considered as a cellular process associated with memory formation. Furthermore, CPTX was shown to elevate what is called "excitatory transmission." This is to say that the protein acted specifically on synapses that promoted activity of the contacted cell. And finally, CPTX increased the density of so-called dendritic spines. These are tiny bulges in the cell's membrane that are essential for establishing excitatory synaptic connections.

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Further research by the study partners in the UK and Japan revealed that application of CPTX to mice with motor dysfunction -- caused either by spinal cord injury or pathological conditions similar to cerebellar ataxia -- improved the rodent's mobility. And at the cellular level, the drug was shown to repair and promote excitatory synaptic connections.

A molecular connector

CPTX combines functional domains present in natural synaptic organizing proteins in a unique way. The compound was designed to act as a universal bridge builder for excitatory connections between nerve cells. Where two neurons meet, either in adhesive contact or actually in synaptic connection, CPTX links to specific molecules on the surfaces of both involved cells, and thereby either triggers the formation of new synapses or strengthens already existing ones.

"At present, this drug is experimental and its synthesis, the credit for which goes to our UK partners, is quite demanding. We are far off from application in humans," Dityatev emphasized, who in addition to his research at the DZNE is also a member of the Medical Faculty of the University Magdeburg. "However, our study suggests that CPTX can even do better than some of its natural analogs in building and strengthening nerve connections. Thus, CPTX could be the prototype for a new class of drugs with clinical potential." Application would be in disorders that are associated with impaired neuronal connectivity. "Much of the current therapeutic effort against neurodegeneration focuses on stopping disease progression and offers little prospect of restoring lost cognitive abilities. Our approach could help to change this and possibly lead to treatments that actually regenerate neurological functions. Based on the principles we have used in designing CPTX, we thus intend to develop further compounds. In future studies, we want to refine their properties and explore possible therapeutic applications."

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Saturday, August 15, 2020

Hope for chronic pain

Science News
from research organizations

Potential treatment for chronic pain

April 30, 2020
University of Copenhagen The Faculty of Health and Medical Sciences
Researchers have developed a new way to treat chronic pain which has been tested in mice. With a compound designed and developed by the researchers themselves, they can achieve complete pain relief.

Researchers from the University of Copenhagen have developed a new way to treat chronic pain which has been tested in mice. With a compound designed and developed by the researchers themselves, they can achieve complete pain relief.

The treatment has been tested in mice, and the new results have been published in the scientific journal EMBO Molecular Medicine. For more than a decade, the researchers have been working to design, develop and test a drug that shall provide complete pain relief.

"We have developed a new way to treat chronic pain. It is a targeted treatment. That is, it does not affect the general neuronal signalling, but only affects the nerve changes that are caused by the disease," says co-author Kenneth Lindegaard Madsen, Associate Professor at the Department of Neuroscience, University of Copenhagen.

"We have been working on this for more than ten years. We have taken the process all the way from understanding the biology, inventing and designing the compound to describing how it works in animals, affects their behaviour and removes the pain," says Kenneth Lindegaard Madsen.

Chronic pain can occur, among other things, after surgery, in people with diabetes, after a blood clot and after an amputation in the form of phantom pain.

Clinical trials as the next step

The compound developed by the researchers is a so-called peptide named Tat-P4-(C5)2. The peptide is targeted and only affects the nerve changes that pose a problem and cause the pain.

In a previous study, the researchers have shown in an animal model that use of the peptide can also reduce addiction. Therefore, the researchers hope that the compound may potentially help pain patients who have become addicted to, for example, opioid pain relievers in particular.

"The compound works very efficiently, and we do not see any side effects. We can administer this peptide and obtain complete pain relief in the mouse model we have used, without the lethargic effect that characterises existing pain-relieving drugs," says Kenneth Lindegaard Madsen, adding:

"Now, our next step is to work towards testing the treatment on people. The goal, for us, is to develop a drug, therefore the plan is to establish a biotech company as soon as possible so we can focus on this."

The researchers are now working towards clinical trials in collaboration with, among others, pain researcher Nanna Brix Finnerup, Professor at Aarhus University.

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Story Source:

Materials provided by University of Copenhagen The Faculty of Health and Medical SciencesNote: Content may be edited for style and length.


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Wednesday, July 29, 2020

Breakthrough Test for Alzheimer's

New blood test shows great promise in the diagnosis of Alzheimer's disease


July 29, 2020


Lund University


A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study.

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A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer's Association International Conference.

For many years, the diagnosis of Alzheimer's has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer's research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles -- corresponding to the diagnosis of Alzheimer's -- in living people.

"The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting."

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Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute's Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer's disease (ADAD)-causing mutation carriers and non-carriers from the world's largest ADAD cohort.

In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of "intermediate or high likelihood Alzheimer's" (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of "high likelihood Alzheimer's" with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.

In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer's and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer's disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer's) and several other studied blood tests.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer's. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer's. It has the potential to advance the disease's research and care in other important ways.

"Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author on the study.

"While there's more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years."

Alzheimer's is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

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Thursday, July 23, 2020

Covid-19 and the Brain

July 8, 2020


University of Liverpool


Cases of brain complications linked to COVID-19 are occurring across the globe, a new review has shown. The research found that strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease.



Cases of brain complications linked to COVID-19 are occurring across the globe, a new review by University of Liverpool researchers has shown.

Published in The Lancet Neurology, the study found that strokes, delirium and other neurological complications are reported from most countries where there have been large outbreaks of the disease.

COVID-19 has been associated mostly with problems like difficulty breathing, fever and cough. However, as the pandemic has continued, it has become increasingly clear that other problems can occur in patients. These include confusion, stroke, inflammation of the brain, spinal cord, and other kinds of nerve disease.

A recent Liverpool-led study of COVID-19 patients hospitalised in the UK found a range of neurological and psychiatric complications that may be linked to the disease.

To get a sense of the wider picture, the researchers brought together and analysed findings from COVID-19 studies across the globe that reported on neurological complications. The review, which included studies from China, Italy and the USA among others, found almost 1000 patients with COVID-19-associated brain, spinal cord and nerve disease.

Research Fellow, Dr Suzannah Lant, who was working on the project, said: "While these complications are relatively uncommon, the huge numbers of COVID-19 cases globally mean the overall number of patients with neurological problems is likely to be quite large."

One of the complications found to be linked to COVID-19 is encephalitis, which is inflammation and swelling of the brain.

Dr Ava Easton, CEO of the Encephalitis Society, and co-author on the paper said: "It is really important that doctors around the world recognise that COVID-19 can cause encephalitis and other brain problems, which often have potentially devastating, life-changing consequences for patients."

Professor Tom Solomon, senior author on the paper and Director of the Global COVID-Neuro Network, added: "Although such patients are being seen everywhere the virus occurs, many of the reports are lacking in detail. We are currently pooling data from individual patients all around the world, so that we can get a more complete picture. Doctors who would like to contribute patients to this analysis can contact us via the Global COVID-Neuro Network


Wednesday, June 10, 2020

Unexpected uncertainty can breed paranoia

June 9, 2020
Yale University
In times of unexpected uncertainty, such as the sudden appearance of a global pandemic, people may be more prone to paranoia, say researchers.

Silhouette of person, | Credit: © lassedesignen /
Silhouette of person, photo concept (stock image).
Credit: © lassedesignen /

In times of unexpected uncertainty, such as the sudden appearance of a global pandemic, people may be more prone to paranoia, Yale University researchers suggest in a new study published in the journal eLife.

Paranoia is a key symptom of serious mental illness, marked by the belief that other people have malicious intentions. But it also manifests in varying degrees in the general population. For instance, one previous survey found that 20% of the population believed people were against them at some time during the past year; 8% believed that others were actively out to harm them.

The prevailing theory is that paranoia stems from an inability to accurately assess social threats. But Corlett and lead author Erin Reed of Yale hypothesized that paranoia is instead rooted in a more basic learning mechanism that is triggered by uncertainty, even in the absence of social threat.

"We think of the brain as a prediction machine; unexpected change, whether social or not, may constitute a type of threat -- it limits the brain's ability to make predictions," Reed said. "Paranoia may be a response to uncertainty in general, and social interactions can be particularly complex and difficult to predict."

In a series of experiments, they asked subjects with different degrees of paranoia to play a card game in which the best choices for success were changed secretly. People with little or no paranoia were slow to assume that the best choice had changed. However, those with paranoia expected even more volatility in the game. They changed their choices capriciously -- even after a win. The researchers then increased the levels of uncertainty by changing the chances of winning halfway through the game without telling the participants. This sudden change made even the low-paranoia participants behave like those with paranoia, learning less from the consequences of their choices.

In a related experiment, Yale collaborators Jane Taylor and Stephanie Groman trained rats, a relatively asocial species, to complete a similar task where best choices of success changed. Rats who were administered methamphetamine -- known to induce paranoia in humans -- behaved just like paranoid humans. They, too, anticipated high volatility and relied more on their expectations than learning from the task.

Reed, Corlett and their team then used a mathematical model to compare choices made by rats and humans while performing these similar tasks. The results from the rats that received methamphetamine resembled those of humans with paranoia, researchers found.

"Our hope is that this work will facilitate a mechanistic explanation of paranoia, a first step in the development of new treatments that target those underlying mechanisms," Corlett said.

"The benefit of seeing paranoia through a non-social lens is that we can study these mechanisms in simpler systems, without needing to recapitulate the richness of human social interaction," Reed said.


Materials provided by Yale University. Original written by Bill Hathaway. 

Thursday, June 4, 2020

Health Challenges of Social Distancing

Excerpted from the Dana Foundation, March 30, 2020.)

We are social creatures by nature, wired to connect with friends, family, and with other people within their communities (See In Sync: How Humans are Wired for Social Relationships). Yet, according to the U.S. Resources and Services Administration (HRSA), a large number of Americans report feeling lonely or socially isolated from others – so much so that many experts are calling it a “loneliness epidemic.” In response to the COVID-19 pandemic, many communities are facing work and school closures and shelter-in-place orders, which may be further isolating vulnerable populations from the social interactions that are so vital to mental health and well-being.

Here, Myrna Weissman, Ph.D., the Diane Goldman Kemper Family Professor of Epidemiology in Psychiatry at Columbia University’s College of Physicians and Surgeons, discusses the impact of loneliness on mental health, as well as ways to stay connected when circumstances dictate you must stay at home.

What do we know about the effect of social isolation on mental health?

Human attachments are a basic need. That’s why we live in families and communities where we can be connected to other people. It’s just part of the human condition. There is vast data to document that when these kind of attachments are disrupted in early life, like when a mother suffers from post-partum depression, which often disrupts the mother-infant bond, it can have long-term health consequences, ranging from low-birth weight to increased risk of depression, anxiety, substance abuse, or suicidal behavior later in life. Unfortunately, the studies also show that poor bonds early in life can also lead to more social isolation when you are older, as well as feelings of extreme loneliness.

We understand that attachments to others are very important. In fact, a lot of talk therapy focuses on dealing with disruptions to those attachments. You don’t need a lot of friends, but you need to have some people in your life that you can talk to and share your life with.

One of the things psychiatrists were seeing long before the COVID-19 pandemic is that loneliness and social isolation are huge factors in depression. Sometimes, a person has depression and they will avoid other people and become more isolated as their symptoms worsen. Other times, people are depressed because they are isolated from others and they don’t have people they can rely on. Maybe they are lonely because something has changed in their lives. Maybe something bad has happened and they’ve lost someone special. Maybe they don’t get along with their families or the people who should be closest to them. There are, unfortunately, many paths to loneliness....

Does it influence only depression?

No, it influences everything – including chronic medical illnesses like hypertension and diabetes. It’s also now been linked to dementia. People don’t just wake up one day with dementia, unless they’ve had a stroke. Rather, the lack of social interaction, the ability to talk and cooperate with others, leads to a graduate mental decline over time. These social interactions are an important part to health in general.

That said, some people have the opposite experience. They are living with people with whom they don’t get along. Being stuck at home makes things even more stressful as they no longer can do the activities that take them out during the day that can compensate for the underlying discord in the family. That’s of concern.

Then there are the people who live alone. They may be more used to a lowered level of social contact in general. But, on the other hand, many people who live alone have a large number of friends and family members who they see on a regular basis to compensate for that alone time. They could be made more vulnerable by what’s going on, too.

How can people best cope with this sort of forced isolation?

The good news is that human beings, in general, are very flexible and adaptable. There’s good evidence that when you can find ways to connect, it helps to reduce symptoms associated with isolation. Anecdotally, I’ve seen some very creative solutions over the past few weeks....

How can people recognize when the isolation may be becoming too much?

It may not always be easy to recognize it in yourself. It may be easier to see in others. From my experience over the past 10 days, I’d say to watch out for the following situations. First, if there’s someone in your life that you are never hearing from – you send an email or call them and they don’t answer, that’s worrisome. That may be the kind of person who requires more attention during this time. Keep reaching out. Make sure they are okay.

The other kind of situation that may be of concern is a friend or family member who are hyper-focused on the disasters. They are on social media or sending out emails about the number of people who are dying, who are in the hospitals, or the lack of respirators. They are dwelling on the bad things. There, too, it is worthwhile to reach out to them and try to help them focus on something else, to help them see the positives in the situation.

Is there anything we can learn from this period of isolation that can help our mental health and well-being once the isolation from COVID-19 lifts so we can better connect with others in the future?

I’ve been thinking a lot about how the world might change after this is all over. What you take away from this experience will largely depend on your circumstances. Hopefully, you’ll learn something new about yourself. You’ll take stock of what is most vital to your wellbeing during this extraordinary period – both the things you need to be at your best and the things you need to avoid. My hope is that it will help people to reorder their priorities, examine what is important, and discover new ways to foster connections with others.