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.

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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.

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“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.

Having a good listener improves your brain health

 

Your amazing brain in clear language

Having a good listener improves your brain health

Source:

NYU Langone Health / NYU Grossman School of Medicine

Summary:

Researchers find having someone to listen to you when you need to talk is associated with greater cognitive resilience. New study shows social interaction in adulthood can stave off cognitive decline despite brain aging.

    

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Supportive social interactions in adulthood are important for your ability to stave off cognitive decline despite brain aging or neuropathological changes such as those present in Alzheimer's disease, a new study finds.

Your amazing brain in clear language

In the study publishing August 16 in JAMA Network Open, researchers observed that simply having someone available most or all of the time whom you can count on to listen to you when you need to talk is associated with greater cognitive resilience -- a measure of your brain's ability to function better than would be expected for the amount of physical aging- or disease-related changes in the brain, which many neurologists believe can be boosted by engaging in mentally stimulating activities, physical exercise, and positive social interactions. 

"We think of cognitive resilience as a buffer to the effects of brain aging and disease," says lead researcher Joel Salinas, MD, the Lulu P. and David J. Levidow Assistant Professor of Neurology at NYU Grossman School of Medicine and member of the Department of Neurology's Center for Cognitive Neurology. "This study adds to growing evidence that people can take steps, either for themselves or the people they care about most, to increase the odds they'll slow down cognitive aging or prevent the development of symptoms of Alzheimer's disease -- something that is all the more important given that we still don't have a cure for the disease."

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

Date:

August 27, 2020

Source:

DZNE - German Center for Neurodegenerative Diseases

Summary:

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.

    

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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.

Brain essentials in plain language. Click here.

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.

Brain essentials in plain language. Click here.

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."

Brain essentials in plain language. Click here.

Any amount of running linked to significantly lower risk of early death

The brain is at the center of your health. Learn how.

Substantial improvements in population health/longevity

likely if more people took it up, say researchers

November 4, 2019

British Journal of Sports Medicine.

Any amount of running is linked to a significantly lower risk

of death from any cause, finds a pooled analysis

of the available evidence, published online in the

British Journal of Sports Medicine.

If more people took up running -- and they wouldn't have to run far or

fast -- there would likely be substantial improvements in population health and

longevity, conclude the researchers.

It's not clear how good running is for staving off the risk of death from

any cause and particularly from cardiovascular disease and cancer,

say the researchers.

Nor is it clear how much running a person needs to do to reap

these potential benefits, nor whether upping the frequency,

duration, and pace -- in other words, increasing the 'dose' --

might be even more advantageous.

To try and find out, the researchers systematically reviewed relevant

published research, conference presentations, and doctoral theses

and dissertations in a broad range of academic databases.

They looked for studies on the association between running/jogging

and the risk of death from all causes, cardiovascular disease, and cancer.

They found 14 suitable studies, involving 232,149 people,

whose health had been tracked for between 5.5 and 35 years.

During this time, 25,951 of the study participants died.

When the study data were pooled, any amount of running was

associated with a 27% lower risk of death from all causes

for both sexes, compared with no running.

And it was associated with a 30% lower risk of death

from cardiovascular disease, and a 23% lower risk of death from cancer.

Even small 'doses' -- for example, once weekly or less, lasting

less than 50 minutes each time, and at a speed below

6 miles (8 km) an hour, still seemed to be associated

with significant health/longevity benefits.

So running for 25 minutes less than the recommended weekly

duration of vigorous physical activity could reduce the risk of death.

This makes running a potentially good option for those whose main

obstacle to doing enough exercise is lack of time, suggest the researchers.

But upping 'the dose' wasn't associated with a further lowering

of the risk of death from any cause, the analysis showed.

Nevertheless, they suggest that any amount of running is

better than none, concluding: "Increased rates of participation in

running, regardless of its dose, would probably lead to

substantial improvements in population health and longevity."

The brain is at the center of your health. Learn how.

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Story Source:

Materials provided by BMJ. Note: Content may be edited for style and length.

Food, brain health and Alzheimer's

Learn more HERE.

Imagine for a moment that you surmount life's outrageous fortunes and you go over the hurdles, and then you face toward the end of your life the reward for your appropriate and successful aging, the loss of your most human qualities--your ability to reason, make decisions, remember.

That is the fate that my Aunt Barbara faced and a percentage of Americans must deal with. That is, a large fraction of us, if we don't find solutions, ultimately will will suffer the syndrome called Alzheimer's disease.

If you live to 85, you have a 50 per cent chance of getting Alzheimer's.

With the enormous increase in people achieving the age of 65, we cannot allow this disease to become the scourge it already is. Alzheimer's will be much more prevalent in the future by the ironic fact that medical science is helping us live longer.

Now, it is the case that not everyone will suffer this tragic disorder. Currently, experts say that if you live to 85, you will have a 50 per cent chance of getting Alzheimer's.

Researchers and doctors are focused now on making Alzheimer's a treatable condition since indications are that the disease can begin up to 20 years before symptoms such as memory loss manifest themselves.

For example, some scientists believe that a simple test, an exam of the retina (considered part of the brain) by a eye examination, can show early build up of the plaques and tangles that are the hallmark of the disease.

The model of Alzheimer's treatment would be a disease such as diabetes, in which symptoms can be detected and treated with diet, exercise and medications. We treat but don't cure diabetes.

Stroke essentials. Save a life--yours.

May ends and so does Stroke Awareness Month. Get these basics from our book, and learn more about this leading killer of Americans.

Order your copy today!

Barbara Bush: Advocate for literacy and the brain

Former First Lady Barbara Bush, who died on Tuesday, was a strong advocate for reading and literacy. During her time at the White House, Mrs. Bush encouraged reading and writing among Americans. In 1989, she founded the Barbara Bush Foundation for Family Literacy. The foundation started a new children’s program, “My Home Library,” last year, but campaigned to increase the literacy rate of adults as well. Reading is crucial to learning and educational achievement. Reading profoundly supports brain health, through all stages of life. To honor Mrs. Bush’s legacy, we present the following article, “The Reading Brain: How Your Brain Helps You Read, and Why it Matters.”

Adapted from The Reading Brain: How Your Brain Helps You Read, and Why it Matters
by Martha Burns, Ph.D

If you’re reading this, you’re probably an accomplished reader. In fact, you’ve most likely forgotten by now how much work it took you to learn to read in the first place. And you probably never think about what is happening in your brain when you’re reading that email from your boss or this month’s book club selection.

And yet, there’s nothing that plays a greater role in learning to read than a reading-ready brain.

As complex a task as reading is, thanks to developments in neuroscience and technology we are now able to target key learning centers in the brain and identify the areas and neural pathways the brain employs for reading. We not only understand why strong readers read well and struggling readers struggle, but we are also able to assist every kind of reader on the journey from early language acquisition to reading and comprehension—a journey that happens in the brain.

Read about your brain!

We begin to develop the language skills required for reading right from the first gurgles we make as babies. The sounds we encounter in our immediate environment as infants set language acquisition skills in motion, readying the brain for the structure of language-based communication, including reading.

Every time a baby hears speech, the brain is learning the rules of language that generalize, later, to reading.  Even a simple nursery rhyme can help a baby's brain begin to make sound differentiations and create phonemic awareness, an essential building block for reading readiness. By the time a child is ready to read effectively, the brain has done a lot of work coordinating sounds to language, and is fully prepared to coordinate language to reading, and reading to comprehension.

The reading brain can be likened to the real-time collaborative effort of a symphony orchestra, with various parts of the brain working together, like sections of instruments, to maximize our ability to decode the written text in front of us.
….
It’s never too early to set a child on the pathway to becoming a strong reader. And it’s never too late to help a struggling reader strengthen his or her brain to read more successfully and with greater enjoyment.