More effective treatment of Alzheimer’s

Alzheimer's is not an inevitable part of aging. 

Treatments, even cures, may be on the way.

 

Date:

September 30, 2021

Source:

Uppsala University

Summary:

Researchers have designed new antibodies that might provide more effective treatment methods for Alzheimer's disease. By designing antibodies that bind even to the smaller aggregates, or clumps, of the amyloid-beta protein, it may be possible to check the progress of the disease.

FULL STORY

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Researchers at Uppsala University have designed new antibodies that might provide more effective treatment methods for Alzheimer's disease. By designing antibodies that bind even to the smaller aggregates, or clumps, of the amyloid-beta protein, it may be possible to check the progress of the disease.

 

Your amazing brain in clear, everyday language

Healing the Brain: Stress, Trauma and Development

“Easy to read. Difficult to put down.”--Micheal J. Colucciello, Jr., NY State pharmaceutical researcher, retired.

​

“David Balog takes a subject fraught with difficulty and makes it simple and accessible to everyone. The book goes a long way in helping one understand how and why and in what ways stress affects how we live and cope. Invaluable.”--Jessica Hudson, former president, National Association of Former Foster Children

Developing effective treatment methods for Alzheimer's disease has proved difficult. The most effective, which have just been approved, only provide marginal effects. There are several major reasons why they are not effective, one of which is that the antibodies used do not bind to all the types of toxic clumps that cause Alzheimer's disease.

In Alzheimer's disease, the amyloid-beta protein begins to form clumps. This process is called aggregation, and the clumps created are called aggregates. The research group has previously shown that treatment with the peptide somatostatin causes the body to begin breaking down building blocks of the aggregate. In the new study, the researchers use an antibody that can bind to the toxic aggregates to stop them from harming cells.

The problem with the treatment methods currently tested in patient studies is that the antibodies bind much more strongly to large clumps and hardly at all to small clumps. The small clumps are just as toxic as the large ones and many think that they are actually even more dangerous since they can move more.

The purpose of the current study was to develop an antibody format that can bind to both large and small clumps of amyloid-beta. Antibodies use the avidity effect to bind strongly to their targets. This requires the binding of both arms of the antibody to the same target at the same time.

The distance between the arms of the antibody is crucial for how small an aggregate the antibody can bind to strongly. If the aggregate is smaller than the distance between the arms, they do not bind to the aggregate strongly. If it is larger, they bind to the aggregate very strongly. In the new article, the researchers have developed a new antibody format with shorter distances between the arms so that they bind to smaller aggregates. The new format also has more binding sites to make the binding extra strong.

"Thanks to the avidity effect, the new antibody format is at least 40 times stronger in binding to the clumps. The new type of antibody can also bind to small aggregates with avidity, which we have not previously seen any other antibody do. That is fantastic," says Greta Hultqvist, Senior lecturer and Associate Professor in Protein drug design at Uppsala University who led the study.

The effects of the antibodies were also tested in a cell culture experiment, which showed that the new antibody format could save cells from death caused by amyloid-beta aggregates. Although no pre-clinical experiments were included, the team thinks their results suggest that the new antibody design could be more effective than those trialled so far.

"The focus of the study was targeting the amyloid-beta protein in Alzheimer's disease, but the new antibody design can be general and applicable to other disease-causing clumps. From a long-term perspective, we hope that the new format can open up new avenues for the generation of future treatments, not only in Alzheimer's disease, but also other diseases where proteins start to form aggregates, like Parkinson's disease," says Fadi Rofo, doctoral student and first author of the study.

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Story Source:

Materials provided by Uppsala University. Original written by Elin Bäckström. Note: Content may be edited for style and length.

Likely cause of Alzheimer’s disease identified

 

A likely cause of Alzheimer's disease.

Date:

September 15, 2021

Source:

Curtin University

Summary:

Ground-breaking new research has discovered a likely cause of Alzheimer's disease, in a significant finding that offers potential new prevention and treatment opportunities.'

    

FULL STORY

Ground-breaking new Curtin University-led research has discovered a likely cause of Alzheimer's disease, in a significant finding that offers potential new prevention and treatment opportunities for the second-leading cause of death.

The study, published in the PLOS Biology journal and tested on mouse models, identified that a probable cause of Alzheimer's disease was the leakage from blood into the brain of fat-carrying particles transporting toxic proteins.

Lead investigator Curtin Health Innovation Research Institute (CHIRI) Director Professor John Mamo said his collaborative group of Australian scientists had identified the probable 'blood-to-brain pathway' that can lead to Alzheimer's disease, the most prevalent form of dementia globally.

 

Your amazing brain in clear, everyday language

Healing the Brain: Stress, Trauma and Development

“Easy to read. Difficult to put down.”--Micheal J. Colucciello, Jr., NY State pharmaceutical researcher, retired.

​

“David Balog takes a subject fraught with difficulty and makes it simple and accessible to everyone. The book goes a long way in helping one understand how and why and in what ways stress affects how we live and cope. Invaluable.”--Jessica Hudson, former president, National Association of Former Foster Children

"While we previously knew that the hallmark feature of people living with Alzheimer's disease was the progressive accumulation of toxic protein deposits within the brain called beta-amyloid, researchers did not know where the amyloid originated from, or why it deposited in the brain," Professor Mamo said.

"Our research shows that these toxic protein deposits that form in the brains of people living with Alzheimer's disease most likely leak into the brain from fat carrying particles in blood, called lipoproteins.

"This 'blood-to-brain pathway' is significant because if we can manage the levels in blood of lipoprotein-amyloid and prevent their leakage into the brain, this opens up potential new treatments to prevent Alzheimer's disease and slow memory loss."

Building on previous award-winning research that showed beta-amyloid is made outside the brain with lipoproteins, Professor Mamo's team tested the ground-breaking 'blood-to-brain pathway' by genetically engineering mouse models to produce human amyloid-only liver that make lipoproteins.

"As we predicted, the study found that mouse models producing lipoprotein-amyloid in the liver suffered inflammation in the brain, accelerated brain cell death and memory loss," Professor Mamo said.

"While further studies are now needed, this finding shows the abundance of these toxic protein deposits in the blood could potentially be addressed through a person's diet and some drugs that could specifically target lipoprotein amyloid, therefore reducing their risk or slowing the progression of Alzheimer's disease."

Alzheimer's WA Chairman Adjunct Professor Warren Harding said the findings may have a significant global impact for the millions of people living with Alzheimer's disease.

Story Source:

Materials provided by Curtin University.

Is memory loss inevitable? Book says No.

From Our Memories, Our Selves.

Learn more here.

From the book:

Learn more here.

A national sleep crisis: Pt. 1

Poor sleep impairs work and productivity, raises risks of car crashes, and may play a key role in risk for developing Alzheimer's disease.

It's serious stuff.

In this excerpt from Healing the Brain: Stress, Trauma and Development, we take a close look at sleep.

Get your copy today on Amazon and Kindle.

Fighting a National Sleep Crisis

Many people view sleep as merely a “down time” when their brains shut off and their bodies rest. People may cut back on sleep, thinking it won’t be a problem, because other responsibilities seem much more important. But research shows that a number of vital tasks carried out during sleep help people stay healthy and function at their best. While you sleep, your brain is hard at work forming the pathways necessary for learning and creating memories and new insights. Without enough sleep, you can’t focus and pay attention or respond quickly. A lack of sleep may even cause mood problems. Also, growing evidence shows that a chronic lack of sleep increases your risk of obesity, diabetes, cardiovascular disease, and infections.

Public Domain Pictures

Researchers acknowledge that regular, consistent sleep plays a major role in brain and body health

Despite growing support for the idea that adequate sleep, like adequate nutrition and physical activity, is vital to our well-being, people are sleeping less. The nonstop “24/7” nature of the world today encourages longer or nighttime work hours and offers continual access to entertainment and other activities. To keep up, people cut back on sleep. A common myth is that people can learn to get by on little sleep (such as less than 6 hours a night) with no adverse effects. Research suggests, however, that adults need at least 7–8 hours of sleep each night to be well rested. Indeed, in 1910, most people slept 9 hours a night. But recent surveys show the average adult now sleeps fewer than 7 hours a night.

Chronic sleep loss or sleep disorders may affect as many as 70 million Americans.

More than one-third of adults report daytime sleepiness so severe that it interferes with work, driving, and social functioning at least a few days each month. Evidence also shows that children’s and adolescents’ sleep is shorter than recommended. These trends have been linked to increased exposure to electronic media. Lack of sleep may have a direct effect on children’s health, behavior, and development. Chronic sleep loss or sleep disorders may affect as many as 70 million Americans. This may result in an annual cost of $16 billion in health care expenses and $50 billion in lost productivity.

What Makes You Sleep? Although you may put off going to sleep in order to squeeze more activities into your day, eventually your need for sleep becomes overwhelming. This need appears to be due, in part, to two substances your body produces. One substance, called adenosine, builds up in your blood while you’re awake. Then, while you sleep, your body breaks down the adenosine. Levels of this substance in your body may help trigger sleep when needed.

A buildup of adenosine and many other complex factors might explain why, after several nights of less than optimal amounts of sleep, you build up a sleep debt. This may cause you to sleep longer than normal or at unplanned times during the day. Because of your body’s internal processes, you can’t adapt to getting less sleep than your body needs. Eventually, a lack of sleep catches up with you. The other substance that helps make you sleep is a hormone called melatonin. This hormone makes you naturally feel sleepy at night. It is part of your internal “biological clock,” which controls when you feel sleepy and your sleep patterns. Your biological clock is a small bundle of cells in your brain that works throughout the day and night. Internal and external environmental cues, such as light signals received through your eyes, control these cells. Your biological clock triggers your body to produce melatonin, which helps prepare your brain and body for sleep. As melatonin is released, you’ll feel increasingly drowsy. 

Get your copy today on Amazon and Kindle.

Fi

Foods to prevent obesity, Alzheimer's, stroke

Source: Penn State

Summary:

The reason why some people find it so hard to resist finishing an entire bag of chips or bowl of candy may lie with how their brain responds to food rewards, according to researchers who found that when certain regions of the brain reacted more strongly to being rewarded with food than being rewarded with money, those people were more likely to overeat.

 Learn about your brain and food.    

FULL STORY

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The reason why some people find it so hard to resist finishing an entire bag of chips or bowl of candy may lie with how their brain responds to food rewards, leaving them more vulnerable to overeating.

In a study with children, researchers found that when certain regions of the brain reacted more strongly to being rewarded with food than being rewarded with money, those children were more likely to overeat, even when the child wasn't hungry and regardless of if they were overweight or not.

Shana Adise, a postdoctoral fellow at the University of Vermont who led the study while earning her doctorate at Penn State, said the results give insight into why some people may be more prone to overeating than others. The findings may also give clues on how to help prevent obesity at a younger age.

"If we can learn more about how the brain responds to food and how that relates to what you eat, maybe we can learn how to change those responses and behavior," Adise said. "This also makes children an interesting population to work with, because if we can stop overeating and obesity at an earlier age, that could be really beneficial."

"Until we know the root cause of overeating and other food-related behaviors, it's hard to give good advice on fixing those behaviors," Keller said. "Once patterns take over and you overeat for a long time, it becomes more difficult to break those habits. Ideally, we'd like to prevent them from becoming habits in the first place."

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Story Source:

Materials provided by Penn State

Healthy cell structure could stop Alzheimer's

Alzheimer's disease is the most common form of dementia and neurodegeneration worldwide. A major hallmark of the disease is the accumulation of toxic plaques in the brain, formed by the abnormal aggregation of a protein called beta-amyloid inside neurons.

Still without cure, Alzheimer's poses a significant burden on public health systems. Most treatments focus on reducing the formation of amyloid plaques, but these approaches have been inconclusive. As a result, scientists are now searching for alternative treatment strategies, one of which is to consider Alzheimer's as a metabolic disease.

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Taking this line of thought, Johan Auwerx's lab at EPFL looked at mitochondria, which are the energy-producing powerhouses of cells, and thus central in metabolism. Using worms and mice as models, they discovered that boosting mitochondria defenses against a particular form of protein stress, enables them to not only protect themselves, but to also reduce the formation of amyloid plaques.

During normal aging and age-associated diseases such as Alzheimer's, cells face increasing damage and struggle to protect and replace dysfunctional mitochondria. Since mitochondria provide energy to brain cells, leaving them unprotected in Alzheimer's disease favors brain damage, giving rise to symptoms like memory loss over the years.

The scientists identified two mechanisms that control the quality of mitochondria: First, the "mitochondrial unfolded protein response" (UPRmt), which protects mitochondria from stress stimuli. Second, mitophagy, a process that recycles defective mitochondria. Both these mechanisms are the key to delaying or preventing excessive mitochondrial damage during disease.

While we have known for a while that mitochondria are dysfunctional in the brains of Alzheimer's patients, this is the first evidence that they actually try to fight the disease by boosting quality control pathways. "These defense and recycle pathways of the mitochondria are essential in organisms, from the worm C. elegans all the way to humans," says Vincenzo Sorrentino, first author of the paper. "So we decided to pharmacologically activate them."

The team started by testing well-established compounds, such as the antibiotic doxycycline and the vitamin nicotinamide riboside (NR), which can turn on the UPRmt and mitophagy defense systems in a worm model (C. elegans) of Alzheimer's disease. The health, performance and lifespan of worms exposed to the drugs increased remarkably compared with untreated worms. Plaque formation was also significantly reduced in the treated animals.

And most significantly, the scientists observed similar improvements when they turned on the same mitochondrial defense pathways in cultured human neuronal cells, using the same drugs.

The encouraging results led the researchers to test NR in a mouse model of Alzheimer's disease. Just like C. elegans, the mice saw a significant improvement of mitochondrial function and a reduction in the number of amyloid plaques. But most importantly, the scientists observed a striking normalization of the cognitive function in the mice. This has tremendous implications from a clinical perspective.

According to Johan Auwerx, tackling Alzheimer's through mitochondria could make all the difference. "So far, Alzheimer's disease has been considered to be mostly the consequence of the accumulation of amyloid plaques in the brain," he says. "We have shown that restoring mitochondrial health reduces plaque formation -- but, above all, it also improves brain function, which is the ultimate objective of all Alzheimer's researchers and patients."

The strategy provides a novel therapeutic approach to slow down the progression of neurodegeneration in Alzheimer's disease, and possibly even in other disorders such as Parkinson's disease, which is also characterized by profound mitochondrial and metabolic defects.

The approach remains to be tested in human patients. "By targeting mitochondria, NR and other molecules that stimulate their 'defense and recycle' systems could perhaps succeed where so many drugs, most of which aim to decrease amyloid plaque formation, have failed," says Vincenzo Sorrentino.

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Story Source:

Materials provided by Ecole Polytechnique Fédérale de Lausanne.

Foods that May Prevent Alzheimer's

Source: Web MD: 

The MIND Diet

 

Want another great reason to eat healthy? The food choices you make daily might lower your odds of getting Alzheimer’s disease, some scientists say.

Researchers have found that people who stuck to a diet that included foods like berries, leafy greens, and fish had a major drop in their risk for the memory-sapping disorder, which affects more than 5 million Americans over age 65.

The eating plan is called the MIND diet. Here’s how it works.

Brain-Friendly Foods

MIND stands for Mediterranean-DASH Intervention for Neurodegenerative Delay. It’s similar to two other healthy meal plans: the DASH diet and the Mediterranean diet. 

But the MIND approach “specifically includes foods and nutrients that medical literature and data show to be good for the brain, such as berries,” says Martha Clare Morris, ScD, director of nutrition and nutritional epidemiology at Rush University Medical Center.

You eat things from these 10 food groups:

• Green leafy vegetables (like spinach and salad greens): At least six servings a week
• Other vegetables: At least one a day
• Nuts: Five servings a week
• Berries: Two or more servings a week
• Beans: At least three servings a week
• Whole grains: Three or more servings a day
• Fish: Once a week
• Poultry (like chicken or turkey): Two times a week
• Olive oil: Use it as your main cooking oil.
• Wine: One glass a day

You avoid:

• Red meat: Less than four servings a week
• Butter and margarine: Less than a tablespoon daily
• Cheese: Less than one serving a week
• Pastries and sweets: Less than five servings a week
• Fried or fast food: Less than one serving a week

The Benefits

One study showed that people who stuck to the MIND diet lowered their risk of Alzheimer’s disease by 54%. That’s big. But maybe even more importantly, researchers found that adults who followed the diet only part of the time still cut their risk of the disease by about 35%.

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