Posts Tagged ‘neurodegeneration’

A promising molecule has offered hope for a new treatment that could stop or slow Parkinson’s, something no treatment can currently do.

Researchers from the University of Helsinki found that molecule BT13 has the potential to both boost levels of dopamine, the chemical that is lost in Parkinson’s, as well as protect the dopamine-producing brain cells from dying.

The results from the study, co-funded by Parkinson’s UK and published online today in the journal Movement Disorders, showed an increase in dopamine levels in the brains of mice following the injection of the molecule. BT13 also activated a specific receptor in the mouse brains to protect the cells.

Typically, by the time people are diagnosed with Parkinson’s, they have already lost 70-80 per cent of their dopamine-producing cells, which are involved in coordinating movement.

While current treatments mask the symptoms, there is nothing that can slow down its progression or prevent more brain cells from being lost, and as dopamine levels continue to fall, symptoms get worse and new symptoms can appear.

Researchers are now working on improving the properties of BT13 to make it more effective as a potential treatment which, if successful, could benefit the 145,000 people living with Parkinson’s in the UK.

The study builds on previous research on another molecule that targets the same receptors in the brain, glial cell line-derived neurotrophic factor (GDNF), an experimental treatment for Parkinson’s which was the subject of a BBC documentary in February 2019. While the results were not clear cut, GDNF has shown promise to restore damaged cells in Parkinson’s.

However, the GDNF protein requires complex surgery to deliver the treatment to the brain because it’s a large molecule that cannot cross the blood-brain barrier – a protective barrier that prevents some drugs from getting into the brain.

BT13, a smaller molecule, is able to cross the blood-brain barrier – and therefore could be more easily administered as a treatment, if shown to be beneficial in further clinical trials.

Professor David Dexter, Deputy Director of Research at Parkinson’s UK, said:

“People with Parkinson’s desperately need a new treatment that can stop the condition in its tracks, instead of just masking the symptoms.

“One of the biggest challenges for Parkinson’s research is how to get drugs past the blood-brain barrier, so the exciting discovery of BT13 has opened up a new avenue for research to explore, and the molecule holds great promise as a way to slow or stop Parkinson’s.

“More research is needed to turn BT13 into a treatment to be tested in clinical trials, to see if it really could transform the lives of people living with Parkinson’s.”

Dr Yulia Sidorova, lead researcher on the study, said: “We are constantly working on improving the effectiveness of BT13. We are now testing a series of similar BT13 compounds, which were predicted by a computer program to have even better characteristics.

“Our ultimate goal is to progress these compounds to clinical trials in a few coming years.”

Molecule offers hope for halting Parkinson’s

Researchers at the University of Southern California looked at more than 17,000 brain scans to see if daily smoking and drinking advanced brain age. The study found that every gram of alcohol consumed a day aged the brain by 11 days. Smoking a pack of cigarettes a day for a year aged the brain by 11 days. It is one of the largest studies ever done on brain aging and alcohol, making the findings quite robust.

by Shira Feder

Over time, drinking a little bit more alcohol than recommended could accelerate the brain’s aging process, according to a new study.

Though previous studies have found the same, most were tentative findings based on small groups of people or large groups of mice.

The new study, from researchers at the University of Southern California, offers a more robust estimate, reached by examining 17,308 human brain scans from the UK Biobank — one of the biggest sample sizes ever seen.

The team found that for every gram of alcohol consumed a day, the brain aged 0.02 years — or, seven-and-a-half days. (The average can of beer or small glass of wine contains 14 grams of alcohol). People who reported drinking every day had brains which were, on average, 0.4 years older than people who didn’t drink daily.

Smoking had even stronger effect: the team found that those who smoke a pack of cigarettes a day for a year age their brains by 0.03 years (11 days).

The researchers took 30% of the brain scans in their study, all from people aged 45 to 81, and used them to train a computer, which scanned each brain to see how old or young they looked.

They then compared the computer’s estimates of each brain’s age with the person’s real age, and their self-reports of how much alcohol and tobacco they consume daily, in order to see if consuming alcohol or tobacco regularly aged the brain.

Comparing those results with the other 70% of their brain scans, they found that the more you drank and smoke, the more likely you were to have a brain aged beyond your actual age.

Lucina Uddin, director of the Cognitive and Behavioral Neuroscience Division at the University of Miami, who was not involved in the study, told Insider that the use of an algorithm is what makes this study’s findings so compelling.

“Back in the day we’d scan 20 or 40 subjects, if we were lucky, for neuroimaging studies,” Uddin said. “Now we’re getting bigger numbers like 200 or 300 individuals. But this is the biggest sample we’ve ever seen.”

Because the sample size is so big, scientists can ask questions that apply to the entire population, rather than just a few people.

Brain age is essentially a measure of brain health, says Uddin, who was not surprised by the study’s findings.

“Looking at brain age is a way of checking how well you’ve been taking care of your brain,” she told Insider. “My age is 40, but does my brain look more like a 50-year-old brain or a 60-year-old brain? Do you look younger than your age or older than your age?”

The lead author of the study, Arthur Toga, told Inverse: “The 0.4 years of difference was statistically significant. We suggest that daily or almost daily alcohol consumption can be detrimental to the brain.”

However, many super-agers — people who live well beyond 100 years old, and often appear resistant to the dementia gene — report drinking alcohol now and then.

What’s more, a recent Harvard study found drinking in moderation can have some benefits, particularly for the heart.

Dr. Qi Sun, a co-author of the Harvard study, previously told Insider: “If you drink alcohol, it’s very important that you drink responsibly, not in excess, and that you also focus on eating a healthy diet, maintaining a healthy body weight, not smoking, and exercising. If you don’t drink you don’t need to start drinking.”

https://www.insider.com/alcohol-every-day-ages-your-brain-quicker-17000-brain-scans-2020-1


Dr. Moir’s radical and iconoclastic theories defied conventional views of the disease. But some scientists were ultimately won over.

By Gina Kolata

Robert D. Moir, a Harvard scientist whose radical theories of the brain plaques in Alzheimer’s defied conventional views of the disease, but whose research ultimately led to important proposals for how to treat it, died on Friday at a hospice in Milton, Mass. He was 58.

His wife, Julie Alperen, said the cause was glioblastoma, a type of brain cancer.

Dr. Moir, who grew up on a farm in Donnybrook, a small town in Western Australia, had a track record for confounding expectations. He did not learn to read or write until he was nearly 12; Ms. Alperen said he had told her that the teacher at his one-room schoolhouse was “a demented nun.” Yet, she said, he also knew from age 7 that he wanted to be a scientist.

Dr. Moir succeeded in becoming a researcher who was modest and careful, said his Ph.D. adviser, Dr. Colin Masters, a neuropathologist at the University of Melbourne. So Dr. Masters was surprised when Dr. Moir began publishing papers proposing an iconoclastic rethinking of the pathology of Alzheimer’s disease.

Dr. Moir’s hypothesis “was and is a really novel and controversial idea that he alone developed,” Dr. Masters said.

“I never expected this to come from this quiet achiever,” he said.

Dr. Moir’s theory involved the protein beta amyloid, which forms plaques in the brains of Alzheimer’s patients.

Conventional wisdom held that beta amyloid accumulation was a central part of the disease, and that clearing the brain of beta amyloid would be a good thing for patients.

Dr. Moir proposed instead that beta amyloid is there for a reason: It is the way the brain defends itself against infections. Beta amyloid, he said, forms a sticky web that can trap microbes. The problem is that sometimes the brain goes overboard producing it, and when that happens the brain is damaged.

The implication is that treatments designed to clear the brain of amyloid could be detrimental. The goal would be to remove some of the sticky substance, but not all of it.

The idea, which Dr. Moir first proposed 12 years ago, was met with skepticism. But he kept at it, producing a string of papers with findings that supported the hypothesis. Increasingly, some of the doubters have been won over, said Rudolph Tanzi, a close friend and fellow Alzheimer’s researcher at Harvard.

Dr. Moir’s unconventional ideas made it difficult for him to get federal grants. Nearly every time he submitted a grant proposal to the National Institutes of Health, Dr. Tanzi said in a phone interview, two out of three reviewers would be enthusiastic, while a third would simply not believe it. The proposal would not be funded.

But Dr. Moir took those rejections in stride.

“He’d make a joke about it,” Dr. Tanzi said. “He never got angry. I never saw Rob angry in my life. He’d say, ‘What do we have to do next?’ He was always upbeat, always optimistic.”

Dr. Moir was supported by the Cure Alzheimer’s Fund, and he eventually secured some N.I.H. grants.

Dr. Moir first came to the United States in 1994, when Dr. Tanzi was looking for an Alzheimer’s biochemist to work in his lab. Working with the lab as a postdoctoral fellow and later as a faculty member with his own lab, Dr. Moir made a string of major discoveries about Alzheimer’s disease.

For example, Dr. Moir and Dr. Tanzi found that people naturally make antibodies to specific forms of amyloid. These antibodies protect the brain from Alzheimer’s but do not wipe out amyloid completely. The more antibodies a person makes, the greater the protection against Alzheimer’s.

That finding, Dr. Tanzi said, inspired the development of an experimental drug, which its manufacturer, Biogen, says is helping to treat some people with Alzheimer’s disease. Biogen plans to file for approval from the Food and Drug Administration.

Robert David Moir was born on April 2, 1961, in Kojonup, Australia, to Mary and Terrence Moir, who were farmers. He studied the biochemistry of Alzheimer’s disease at the University of Western Australia before joining Dr. Tanzi’s lab.

Once he learned to read, Ms. Alperen said, he never stopped — he read science fiction, the British magazine New Scientist and even PubMed, the federal database of scientific publications.

“Rob had an encyclopedic knowledge of the natural world,” she said.

He shared that love with his family, on frequent hikes and on trips with his young children to look for rocks, insects and fossils. He also played Australian-rules football, which has elements of rugby as well as American football, and helped form the Boston Demons Australian Rules Football Team in 1997, his wife said.

In addition to his wife, with whom he lived in Sharon, Mass., Dr. Moir’s survivors include three children, Alexander, Maxwell and Holly Moir; a brother, Andrew; and a sister, Catherine Moir. His marriage to Elena Vaillancourt ended in divorce.

Pioneering aerosol writer Lonny Wood, better known by his moniker, Phase 2, has died. He is remembered for his invaluable, media-spanning contributions to hip-hop and is acknowledged as the first artist to perfect the “softie” style of aerosol calligraphy, characterized by its marshmallow-like bubbled lettering.

Born in the Bronx, New York, Phase 2 began tagging subway trains in the early 1970s, becoming one of the most widely emulated stylists of that moment. As his work matured, he progressively abstracted and complicated his calligraphy, “deconstructing the letter”—in the words of hip-hop journalist Jeff Chang—“into hard lines, third eyes, horns, drills, spikes, arches, Egyptian pharos and dogs, pure geometrics.” Phase 2 was an early member of United Graffiti Artists (UGA), a collective of train painters credited with mounting the first gallery show of so-called graffiti art, a term Wood rejected for devaluing and criminalizing his work and that of his peers.

In addition to his calligraphic work, Phase 2 rapped, DJ’ed, and was a member of the New York City Breakers, a pioneering break-dancing crew. As a graphic artist, he lent his hard-edge geometric style—influenced by the Bronx’s many Art Deco theaters—to flyers promoting significant parties and shows like 1982’s Kool Lady Blue at the Roxy nightclub in Chelsea, which established a rapport between hip-hop and New York’s contemporaneous punk and New Wave scenes. In the mid-’80s, he served as the art director of the underground zine International Graffiti Times, often cited as the first publication devoted to street and subway art. In 1996, he and International Graffiti Times editor David Schmidlapp copublished the book Style: Writing from the Underground, a history of aerosol art. In recent decades, his work has been featured in numerous exhibitions of urban art.

“I’m absorbing and devouring language,” Phase 2 said of his work “and creating something else with it. . . . The English language isn’t much, especially in its current state. By comparison (to Chinese and Japanese) it’s like a dot. Why not go beyond that and just create an alphabet or language? You can’t put a limit on communication or how one can communicate, you’ve always got to look further, that’s how style expanded in the first place.”

https://www.artforum.com/news/phase-2-1955-2019-81607

Young carriers of the APOE4 allele have brains that are more connected (left, red lines illustrate connections between brain areas) and active (right, yellow indicates activity) than the brains of those without the allele.
KRISHNA SINGH, ELIFE, 8:E36011, 2019.

A growing body of evidence supports the theory that neural hyperactivity and hyperconnectivity precede the pathological changes that lead to neurodegeneration.

DIANA KWON

There are approximately 5.6 million people over the age of 65 living with Alzheimer’s disease in the United States. With the population aging, that number is projected to grow to 7.1 million by 2025. Researchers know that age, a family history of the disease, and carrying a genetic variant known as APOE4 are all associated with a higher chance of developing the condition. But the biological mechanisms leading to Alzheimer’s are still largely a mystery.

Over the last decade, scientists have amassed evidence for a hypothesis that, prior to developing full-blown Alzheimer’s disease, patients experience a period of hyperactivity and hyperconnectivity in the brain. Several functional magnetic resonance imaging studies have reported that people with mild cognitive impairment (MCI), a condition that often precedes Alzheimer’s, appear to have higher brain activity levels than their age-matched counterparts. Researchers have also found signs of such changes in healthy people carrying the APOE4 allele, as well as in presymptomatic stages of Alzheimer’s in rodent models of the disease.

Krishna Singh, a physicist and imaging neuroscientist at the Cardiff University Brain Research Imaging Center (CUBRIC) in the UK, and his colleagues wanted to investigate this theory further. Previous studies of brain activity in young APOE4 carriers were mostly conducted using small sample sizes, according to Singh. But by the mid-2010s, his team had access to neuroimaging data from close to 200 participants studied at CUBRIC as part of an effort to build a massive dataset of healthy brains. So the researchers decided to use the data to search for signs of unusual brain activity and connectivity in people with the APOE4 allele.

Using magnetoencephalography (MEG), a neuroimaging technique that records the magnetic fields generated by electrical activity in the brain, Singh and his colleagues had measured resting-state brain activity in a group of 183 healthy adults, which included 51 individuals who carried at least one copy of APOE4. The average age of the participants was 24 years old, although ages ranged from 18 to 65 years old.

Analysis of the imaging data revealed that, compared with controls, young APOE4 carriers displayed greater activity in several regions in the right side of the brain, including parts of what’s known as the default mode network, which is active when a person is not focused on a specific task. A similar set of brain regions also showed an overall increase in connectivity.

The researchers next compared the results to brain activity and connectivity data from a previous neuro­imaging study they had conducted, which found that elderly people with early-stage Alzheimer’s disease had decreased neuronal activity and connectivity compared with that of age-matched controls. The network of brain areas that displayed increased connectivity in young APOE4 carriers, the team found, partially overlapped with the brain regions that exhibited a decrease in connectivity in people with early-stage Alzheimer’s. These findings are intriguing, Singh says, because they suggest that brain areas that end up getting impaired in Alzheimer’s may be highly active and connected early in life—long before symptoms of the disease appear.

“This study adds further evidence that hyperactivity and hyperconnectivity may play an influential role in Alzheimer’s disease,” says Tal Nuriel, a professor of pathology and cell biology at the Columbia University Medical Center who wasn’t involved in the work. Because this was an observational study, the findings can only establish a correlation between brain activity and Alzheimer’s, Nuriel adds, so it’s still unclear whether the hyperactivity and hyperconnectivity observed during the early stages of the disease are a cause or a consequence of pathological changes that lead to neurodegeneration.

Scientists used to think that increased activity was simply a compensatory effect—the brain trying to make up for a loss of neurons and synapses, says Willem de Haan, a neurologist at the Amsterdam University Medical Center who was not involved in the latest study. “But I think there’s overwhelming evidence that this may actually be pathological hyperactivity.”

Much of that evidence comes from animal experiments conducted over the last decade or so. In rodents, researchers have found that hyperactivity can increase the production and spread of amyloid-ß, the peptide that accumulates into plaques found in the brains of people with Alzheimer’s—and that amyloid-ß can in turn induce neuronal hyperactivity. These findings have led some scientists to speculate that there might be a self-amplifying loop, where a progressive hyperactivity and build-up of amyloid-ß drives pathological changes associated with the neurodegenerative disease.

Research in humans also supports the idea that hyperactivity could play a causal role in Alzheimer’s disease. In 2012, researchers at Johns Hopkins University treated individuals with MCI with the anti-epileptic drug levetiracetam and found that the therapy suppressed activity in the hippocampus and led to improved memory performance. The team is currently testing levetiracetam for MCI in clinical trials. “I think this is one of the most interesting results,” says de Haan. “It seems to show that by correcting hyperactivity we can actually find some improvements in patients that might point to a completely new type of therapy for [Alzheimer’s disease].”

For the current study, Singh’s team also trained a machine-learning algorithm to distinguish APOE4 carriers from non-carriers based on their MEG data and tested whether it would be able to predict cases of Alzheimer’s. They found that while the program was able to perform above chance, the effect was not significant. “In a way, that was kind of encouraging,” Singh says. “Because I don’t think anybody would predict that we could find a signature [for Alzheimer’s] in 20- and 30-year-olds.”

For now, Singh says, his team’s findings simply shed light on what might be going on in the brains of people with the APOE4 allele. There are still a number of unanswered questions—such as when the transition from hyper- to hypoconnectivity and activity happens, what changes occur in the largely understudied middle-aged cohort, and whether there are differences between APOE4 carriers who go on to develop Alzheimer’s and those who don’t. Ultimately, to understand how disruptions in neuronal activity lead to behavioral and cognitive deficits, scientists need to decipher what’s going on inside a healthy brain, Singh says. “[We] require a model of how the brain works—and those are still in their infancy.”

https://www.the-scientist.com/notebook/genetic-risk-for-alzheimers-disease-linked-to-highly-active-brains-66483?utm_campaign=TS_DAILY%20NEWSLETTER_2019&utm_source=hs_email&utm_medium=email&utm_content=78081371&_hsenc=p2ANqtz-98aZf5axxCqtPYITNqfIVWKM6xuk3ni-QSpgTS4gFXzeQcntecrOf6DFFXjrf5qcktWTUz2M3xnAEJlvXTaS7WDQEKNg&_hsmi=78081371

A technology that originated at the University of Minnesota is well on its way to commercialization thanks to an investment award from Alzheimer’s Drug Discovery Foundation (ADDF).

The investment of up to $500,000 was awarded through the ADDF’s Diagnostics Accelerator initiative. Toronto, Ontario-based RetiSpec licensed through the University of Minnesota’s Technology Commercialization program. The technology harnesses hyperspectral imaging and machine learning.

“We are focused on bringing to market a noninvasive, easy-to-use, screening technology that can change when and how we detect Alzheimer’s disease at its earliest stages including before a patient presents with symptoms,” said Eliav Shaked, CEO of RetiSpec. “Early detection provides an important window of opportunity for timely therapeutic interventions that can slow or even prevent the progression of Alzheimer’s disease. ADDF’s investment represents another point of external validation of the promise of our technology.”

In preclinical studies and a pilot human study, the retinal imaging technology was effective in detecting small changes in biomarkers associated with elevated cerebral amyloid beta levels early in the disease process including before the onset of clinical symptoms.

RetiSpec is currently collaborating with Toronto Memory Program, Canada’s largest Alzheimer’s clinical trial site, to validate the accuracy and usability of the technology in patients.

“We believe that RetiSpec’s retinal scanner stands out and shows promise as a unique diagnostic tool among a range of technologies in development,” said Howard Fillit , MD, founding executive director and chief science officer of ADDF The technology has the potential to facilitate early diagnosis, improve the lives of patients and their loved ones and save the healthcare system money and resources. The technology will also be useful in making clinical trials for Alzheimer’s disease more efficient.”

https://www.mddionline.com/feast-your-eyes-new-technology-early-alzheimers-screening


Brain tissue from deceased patients with Alzheimer’s has more tau protein buildup (brown spots) and fewer neurons (red spots) as compared to healthy brain tissue.

By Yasemin Saplakoglu

Alzheimer’s disease might be attacking the brain cells responsible for keeping people awake, resulting in daytime napping, according to a new study.

Excessive daytime napping might thus be considered an early symptom of Alzheimer’s disease, according to a statement from the University of California, San Francisco (UCSF).

Some previous studies suggested that such sleepiness in patients with Alzheimer’s results directly from poor nighttime sleep due to the disease, while others have suggested that sleep problems might cause the disease to progress. The new study suggests a more direct biological pathway between Alzheimer’s disease and daytime sleepiness.

In the current study, researchers studied the brains of 13 people who’d had Alzheimer’s and died, as well as the brains from seven people who had not had the disease. The researchers specifically examined three parts of the brain that are involved in keeping us awake: the locus coeruleus, the lateral hypothalamic area and the tuberomammillary nucleus. These three parts of the brain work together in a network to keep us awake during the day.

The researchers compared the number of neurons, or brain cells, in these regions in the healthy and diseased brains. They also measured the level of a telltale sign of Alzheimer’s: tau proteins. These proteins build up in the brains of patients with Alzheimer’s and are thought to slowly destroy brain cells and the connections between them.

The brains from patients who had Alzheimer’s in this study had significant levels of tau tangles in these three brain regions, compared to the brains from people without the disease. What’s more, in these three brain regions, people with Alzheimer’s had lost up to 75% of their neurons.

“It’s remarkable because it’s not just a single brain nucleus that’s degenerating, but the whole wakefulness-promoting network,” lead author Jun Oh, a research associate at UCSF, said in the statement. “This means that the brain has no way to compensate, because all of these functionally related cell types are being destroyed at the same time.”

The researchers also compared the brains from people with Alzheimer’s with tissue samples from seven people who had two other forms of dementia caused by the accumulation of tau: progressive supranuclear palsy and corticobasal disease. Results showed that despite the buildup of tau, these brains did not show damage to the neurons that promote wakefulness.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh said in the statement. “Understanding why this is the case is something we need to follow up in future research.”

Though amyloid proteins, and the plaques that they form, have been the major target in several clinical trials of potential Alzheimer’s treatments, increasing evidence suggests that tau proteins play a more direct role in promoting symptoms of the disease, according to the statement.

The new findings suggest that “we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments,” senior author Dr. Lea Grinberg, an associate professor of neurology and pathology at the UCSF Memory and Aging Center, said in the statement.

The findings were published Monday (Aug. 12) in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

https://www.livescience.com/alzheimers-attacks-wakefulness-neurons.html?utm_source=notification