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

---

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.

---

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.

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.

    

FULL STORY

---

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."

One lifestyle may hold a key to slowing down aging

Your amazing brain in clear language.

Tsimane people are unique for their healthy brains that age more slowly

Date:

May 26, 2021

Source:

University of Southern California

Summary:

The Tsimane indigenous people of the Bolivian Amazon experience less brain atrophy than their American and European peers. The decrease in their brain volumes with age is 70% slower than in Western populations.

    

FULL STORY

A team of international researchers has found that the Tsimane indigenous people of the Bolivian Amazon experience less brain atrophy than their American and European peers. The decrease in their brain volumes with age is 70% slower than in Western populations. Accelerated brain volume loss can be a sign of dementia.

The study was published May 26, 2021 in the Journal of Gerontology, Series A: Biological Sciences and Medical Sciences.

Although people in industrialized nations have access to modern medical care, they are more sedentary and eat a diet high in saturated fats. In contrast, the Tsimane have little or no access to health care but are extremely physically active and consume a high-fiber diet that includes vegetables, fish and lean meat.

"The Tsimane have provided us with an amazing natural experiment on the potentially detrimental effects of modern lifestyles on our health," said study author Andrei Irimia, an assistant professor of gerontology, neuroscience and biomedical engineering at the USC Leonard Davis School of Gerontology and the USC Viterbi School of Engineering. "These findings suggest that brain atrophy may be slowed substantially by the same lifestyle factors associated with very low risk of heart disease."

Your amazing brain in clear language.

The researchers enrolled 746 Tsimane adults, ages 40 to 94, in their study. To acquire brain scans, they provided transportation for the participants from their remote villages to Trinidad, Bolivia, the closest town with CT scanning equipment. That journey could last as long as two full days with travel by river and road.

The team used the scans to calculate brain volumes and then examined their association with age for Tsimane. Next, they compared these results to those in three industrialized populations in the U.S. and Europe.

The scientists found that the difference in brain volumes between middle age and old age is 70% smaller in Tsimane than in Western populations. This suggests that the Tsimane's brains likely experience far less brain atrophy than Westerners as they age; atrophy is correlated with risk of cognitive impairment, functional decline and dementia.

The researchers note that the Tsimane have high levels of inflammation, which is typically associated with brain atrophy in Westerners. But their study suggests that high inflammation does not have a pronounced effect upon Tsimane brains.

According to the study authors, the Tsimane's low cardiovascular risks may outweigh their infection-driven inflammatory risk, raising new questions about the causes of dementia. One possible reason is that, in Westerners, inflammation is associated with obesity and metabolic causes whereas, in the Tsimane, it is driven by respiratory, gastrointestinal, and parasitic infections. Infectious diseases are the most prominent cause of death among the Tsimane.

"Our sedentary lifestyle and diet rich in sugars and fats may be accelerating the loss of brain tissue with age and making us more vulnerable to diseases such as Alzheimer's," said study author Hillard Kaplan, a professor of health economics and anthropology at Chapman University who has studied the Tsimane for nearly two decades. "The Tsimane can serve as a baseline for healthy brain aging."

Healthier hearts and -- new research shows -- healthier brains

The indigenous Tsimane people captured scientists' -- and the world's -- attention when an earlier study found them to have extraordinarily healthy hearts in older age. That prior study, published by the Lancet in 2017, showed that Tsimane have the lowest prevalence of coronary atherosclerosis of any population known to science and that they have few cardiovascular disease risk factors. The very low rate of heart disease among the roughly 16,000 Tsimane is very likely related to their pre-industrial subsistence lifestyle of hunting, gathering, fishing, and farming.

"This study demonstrates that the Tsimane stand out not only in terms of heart health, but brain health as well," Kaplan said. "The findings suggest ample opportunities for interventions to improve brain health, even in populations with high levels of inflammation."

Story Source:

Materials provided by University of Southern California. Original written by Jenesse Miller. Note: Content may be edited for style and length.

Your amazing brain in clear language.

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.

    

FULL STORY

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.

Is memory loss inevitable? Book says No.

From Our Memories, Our Selves.

Learn more here.

From the book:

Learn more here.

Does sleep boost memory, affect autism, Alzheimer's?

Learn more about your incredible brain.

Why do we feel great after a solid night's rest and crummy without one?

Are we "brainwashed" during sleep?
Cerebrospinal fluid washes in and out of brain during sleep

Date:

October 31, 2019

Source:

Boston University

Summary:

A new study illustrates that the brain's cerebrospinal fluid pulses during sleep, and that these motions are closely tied with brain wave activity and blood flow. It may confirm the hypothesis that CSF flow and slow-wave activity both help flush toxic, memory-impairing proteins from the brain.

FULL STORY

New research from Boston University suggests that tonight while you sleep, something amazing will happen within your brain. Your neurons will go quiet. A few seconds later, blood will flow out of your head. Then, a watery liquid called cerebrospinal fluid (CSF) will flow in, washing through your brain in rhythmic, pulsing waves.

New research from Boston University suggests that tonight while you sleep, something amazing will happen within your brain. Your neurons will go quiet. A few seconds later, blood will flow out of your head. Then, a watery liquid called cerebrospinal fluid (CSF) will flow in, washing through your brain in rhythmic, pulsing waves.

Learn more about your incredible brain.

"We've known for a while that there are these electrical waves of activity in the neurons," says study coauthor Laura Lewis, a BU College of Engineering assistant professor of biomedical engineering and a Center for Systems Neuroscience faculty member. "But before now, we didn't realize that there are actually waves in the CSF, too."

This research may also be the first-ever study to take images of CSF during sleep. And Lewis hopes that it will one day lead to insights about a variety of neurological and psychological disorders that are frequently associated with disrupted sleep patterns, including autism and Alzheimer's disease.

The coupling of brain waves with the flow of blood and CSF could provide insights about normal age-related impairments as well. Earlier studies have suggested that CSF flow and slow-wave activity both help flush toxic, memory-impairing proteins from the brain. As people age, their brains often generate fewer slow waves. In turn, this could affect the blood flow in the brain and reduce the pulsing of CSF during sleep, leading to a buildup of toxic proteins and a decline in memory abilities. Although researchers have tended to evaluate these processes separately, it now appears that they are very closely linked.

This research may also be the first-ever study to take images of CSF during sleep. And Lewis hopes that it will one day lead to insights about a variety of neurological and psychological disorders that are frequently associated with disrupted sleep patterns, including autism and Alzheimer's disease.

The coupling of brain waves with the flow of blood and CSF could provide insights about normal age-related impairments as well. Earlier studies have suggested that CSF flow and slow-wave activity both help flush toxic, memory-impairing proteins from the brain. As people age, their brains often generate fewer slow waves. In turn, this could affect the blood flow in the brain and reduce the pulsing of CSF during sleep, leading to a buildup of toxic proteins and a decline in memory abilities. Although researchers have tended to evaluate these processes separately, it now appears that they are very closely linked.

Learn more about your incredible brain.

How memories form and fade

Strong memories are encoded by teams of brain cells working together in synchrony

                  

Your remarkable brain in clear, easy-to-read English.

CLICK HERE!

     

   

August 23, 2019:   

California Institute of Technology

Researchers have identified the neural processes that make some memories fade rapidly while other memories persist over time.

                               

                                       

FULL STORY

                   

---

                   

           

Memories in the brain concept (stock image).

Credit: © metamorworks / Adobe Stock

          

Why is it that you can remember the name of your childhood best friend that you haven't seen in years yet easily forget the name of a person you just met a moment ago? In other words, why are some memories stable over decades, while others fade within minutes?               

Using mouse models, Caltech researchers have now determined that strong, stable memories are encoded by "teams" of neurons all firing in synchrony, providing redundancy that enables these memories to persist over time. The research has implications for understanding how memory might be affected after brain damage, such as by strokes or Alzheimer's disease.

The work was done in the laboratory of Carlos Lois, research professor of biology, and is described in a paper that appears in the August 23 of the journal Science. Lois is also an affiliated faculty member of the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech.

Led by postdoctoral scholar Walter Gonzalez, the team developed a test to examine mice's neural activity as they learn about and remember a new place. In the test, a mouse was placed in a straight enclosure, about 5 feet long with white walls. Unique symbols marked different locations along the walls -- for example, a bold plus sign near the right-most end and an angled slash near the center. Sugar water (a treat for mice) was placed at either end of the track. While the mouse explored, the researchers measured the activity of specific neurons in the mouse hippocampus (the region of the brain where new memories are formed) that are known to encode for places.

When an animal was initially placed in the track, it was unsure of what to do and wandered left and right until it came across the sugar water. In these cases, single neurons were activated when the mouse took notice of a symbol on the wall. But over multiple experiences with the track, the mouse became familiar with it and remembered the locations of the sugar. As the mouse became more familiar, more and more neurons were activated in synchrony by seeing each symbol on the wall. Essentially, the mouse was recognizing where it was with respect to each unique symbol.

To study how memories fade over time, the researchers then withheld the mice from the track for up to 20 days. Upon returning to the track after this break, mice that had formed strong memories encoded by higher numbers of neurons remembered the task quickly. Even though some neurons showed different activity, the mouse's memory of the track was clearly identifiable when analyzing the activity of large groups of neurons. In other words, using groups of neurons enables the brain to have redundancy and still recall memories even if some of the original neurons fall silent or are damaged.

Gonzalez explains: "Imagine you have a long and complicated story to tell. In order to preserve the story, you could tell it to five of your friends and then occasionally get together with all of them to re-tell the story and help each other fill in any gaps that an individual had forgotten. Additionally, each time you re-tell the story, you could bring new friends to learn and therefore help preserve it and strengthen the memory. In an analogous way, your own neurons help each other out to encode memories that will persist over time."

Memory is so fundamental to human behavior that any impairment to memory can severely impact our daily life. Memory loss that occurs as part of normal aging can be a significant handicap for senior citizens. Moreover, memory loss caused by several diseases, most notably Alzheimer's, has devastating consequences that can interfere with the most basic routines including recognizing relatives or remembering the way back home. This work suggests that memories might fade more rapidly as we age because a memory is encoded by fewer neurons, and if any of these neurons fail, the memory is lost. The study suggests that one day, designing treatments that could boost the recruitment of a higher number of neurons to encode a memory could help prevent memory loss.

"For years, people have known that the more you practice an action, the better chance that you will remember it later," says Lois. "We now think that this is likely, because the more you practice an action, the higher the number of neurons that are encoding the action. The conventional theories about memory storage postulate that making a memory more stable requires the strengthening of the connections to an individual neuron. Our results suggest that increasing the number of neurons that encode the same memory enables the memory to persist for longer."

Your remarkable brain, in clear, easy-to-read English.

CLICK HERE!