Nine Out of Ten Want to Know Their Brain Disease Risk

Would you take a simple brain health test to learn about your risk of developing a brain disease if you could? According to the global brain health survey, 91% of those questioned would.

This question was asked to more than 27,500 people in the global brain health survey conducted by the Lifebrain project. The survey is led by the Norwegian Institute of Public Health in collaboration with the University of Oslo.

The main findings were:

  • 91% of respondents would definitely or probably take a simple test to learn about the risk of developing a brain disease.
  • 86% would do so even if the disease could not be prevented or treated.

 

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Decreased Proteins, Not Amyloid Plaques, Tied To Alzheimer’s

New research from the University of Cincinnati (UC) bolsters a hypothesis that Alzheimer’s disease is caused by a decline in levels of a specific protein, contrary to a prevailing theory that has been recently called into question.

The prevailing narrative in the field has stated Alzheimer’s is caused by amyloid plaques in the brain, but Alberto Espay, MD, Andrea Sturchio, MD, and their colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic or infectious stress, transform into the abnormal amyloid plaques.

In the current study, the team analyzed the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer’s disease.

What we found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span,” said Espay, professor of neurology in the UC College of Medicine.

Source: https://www.uc.edu/
AND
https://www.eurasiareview.com/

New Alzheimer’s Drug Slows Cognitive Decline by 27%

A new Alzheimer’s drug from Japanese pharmaceutical company Eisai and US drugmaker Biogen has shown promising results in a large-scale clinical trial. The companies announced the trial’s success in a press release, saying their drug — called lecanemab — was observed to have slowed cognitive decline in Alzheimer’s patients by 27% over 18 months.

The companies said 1,795 patients with early-stage Alzheimer’s were randomly selected to receive a placebo treatment or doses of lecanemab every two weeks. Their cognitive decline was then measured on six fronts, including “memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.” According to the statement, lecanemab significantlyreduced clinical decline” over the 18-month timeframe.

Lecanemab, per Eisai, is a monoclonal antibody treatment, which targets toxic amyloid plaques protein clumps that researchers proposed were the cause of the neurodegeneration seen in Alzheimer’s.

The companies noted that around 21% of the patients who received the lecanemab treatment experienced brain swelling that was visible on PET scans.

Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said Michel Vounatsos, Biogen‘s chief executive officer in the companies’ joint press release.

Eisai’s chief executive Haruo Naito said in the company’s press release that the lecanemab study’s success was “an important milestone for Eisai in fulfilling our mission to meet the expectations of the Alzheimer’s disease community.”

Source: https://investors.biogen.com/
AND
https://www.businessinsider.com/

How to Diagnose Alzheimer’s Through Retina

The onset of Alzheimer’s disease can be diagnosed by examining proteins in the retina instead of complicated and invasive PET scans or cerebrospinal fluid analysis. Alzheimer’s disease – the progressive neurological disorder that causes the brain to shrink and brain cells to die – is the most common cause of dementia. The disease causes a continuous decline in thinking, behavior and social skills that affect a person’s ability to function independently.

But while the disorder is incurable, it is important to diagnose it as rapidly as possible so measures can be taken to slow the decline. Doctors hope to eventually develop treatments to reduce the risk of developing Alzheimer’s disease.

But now, doctors in the ophthalmology department of the Samson Assuta-Ashdod University Hospital suggest a much simpler way to diagnose Alzheimer’s – by looking for beta-amyloid plaques and abnormal tau proteins in the retina of the eye. The advantage is the accessibility of the retina for direct visualization by non-invasive means.

The retina is a component of the central nervous system that can easily be accessed by technology used routinely by ophthalmologists, they wrote. Photoreceptors in this “screen” at the back of the eye absorb light and transfer data to the retinal ganglion cell layer. Axons (long, slender nerve fibers) in this layer accumulate along the retinal nerve fiber layer and transfer the data to the brain via the optic nerve connected to the eye.

Since the retina is connected to the brain, it seems that changes in this part of the eye reflect pathological processes in the brain, the authors wrote, including the development of Alzheimer’s disease. Amyloid-beta plaques have been found in the retina of cadavers in autopsies of people who died of Alzheimer’s.

Turmeric is a natural, intensely yellow-colored spice that attaches itself to plaques of amyloid-beta. Ten Alzheimer’s patients and six healthy controls were asked to swallow turmeric capsules. A few days later, their retinas were examined. The yellow spice was found to stick to the retinal cells in Alzheimer’s patients but not in the healthy controlsOther non-invasive tests of the retina – including optical coherence tomography and optical coherence tomography angiography – were also conducted and found to point to the early development of Alzheimer’s, the authors wrote. Still, larger tests must be conducted with these means before they can be implemented clinically. A clear biomarker must also be found in the individual to be sure the patient is developing Alzheimer’s and sent for treatments, they concluded.

The research, just published in the latest issue of Harefuah – the Hebrew-language journal of the Israel Medical Association – was conducted by Drs. Keren Wood of the Samson Assuta Ashdod Hospital and Ben-Gurion University of the Negev, Idit Maharshak of Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Faculty of Medicine, and Yosef Koronyo and Maya Koranyo-Hamaoui of the Cedars-Sinai Medical Center in Los Angeles, California.

Source: https://www.jpost.com/

How to Boost Neuron Production

Researchers at the University of Illinois Chicago have discovered that increasing the production of new neurons in mice with Alzheimer’s disease (AD) rescues the animals’ memory defects. The study, published in the Journal of Experimental Medicine (JEM), shows that new neurons can incorporate into the neural circuits that store memories and restore their normal function, suggesting that boosting neuron production could be a viable strategy to treat AD patients.

New neurons are produced from neural stem cells via a process known as neurogenesis. Previous studies have shown that neurogenesis is impaired in both AD patients and laboratory mice carrying genetic mutations linked to AD, particularly in a region of the brain called the hippocampus that is crucial for memory acquisition and retrieval.

Boosting neurogenesis increases the number of newly formed  neurons involved in storing  and retrieving memories (arrows) in the hoppocampus of mice with Alzheimer’s

However, the role of newly formed neurons in memory formation, and whether defects in neurogenesis contribute to the cognitive impairments associated with AD, is unclear,” says Professor Orly Lazarov of the Department of Anatomy and Cell Biology in the University of Illinois Chicago College of Medicine.

In the new JEM study, Lazarov and colleagues boosted neurogenesis in AD mice by genetically enhancing the survival of neuronal stem cells. The researchers deleted Bax, a gene that plays a major role in neuronal stem cell death, ultimately leading to the maturation of more new neurons. Increasing the production of new neurons in this way restored the animals’ performance in two different tests measuring spatial recognition and contextual memory.

By fluorescently labeling neurons activated during memory acquisition and retrieval, the researchers determined that, in the brains of healthy mice, the neural circuits involved in storing memories include many newly formed neurons alongside older, more mature neurons. These memory-stowing circuits contain fewer new neurons in AD mice, but the integration of newly formed neurons was restored when neurogenesis was increased.

Further analyses of the neurons forming the memory-storing circuits revealed that boosting neurogenesis also increases the number of dendritic spines, which are structures in synapses known to be critical for memory formation, and restores a normal pattern of neuronal gene expression.

Lazarov and colleagues confirmed the importance of newly formed neurons for memory formation by specifically inactivating them in the brains of AD mice. This reversed the benefits of boosting neurogenesis, preventing any improvement in the animals’ memory.

Our study is the first to show that impairments in hippocampal neurogenesis play a role in the memory deficits associated with AD by decreasing the availability of immature neurons for memory formation,” Lazarov says. “Taken together, our results suggest that augmenting neurogenesis may be of therapeutic value in AD patients.

Source: https://www.eurekalert.org/

Reprogramming the Brain’s Cleaning Crew to Mop Up Alzheimer’s Disease

The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco (UCSF). The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases. These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer’s and other brain diseases, said Martin Kampmann, PhD, senior author on the study, which appears in Nature Neuroscience.

Microglia (green) derived from human stem cells

Now, using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs,”  Kampmann said. “This capability presents the opportunity for an entirely new type of therapeutic approach.

Most of the genes known to increase the risk for Alzheimer’s disease act through microglial cells. Thus, these cells have a significant impact on how such neurodegenerative diseases play out, said Kampmann. Microglia act as the brain’s immune system. Ordinary immune cells can’t cross the blood-brain barrier, so it’s the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best. When microglia start losing their way, the result can be brain inflammation and damage to neurons and the networks they form. Under some conditions, for example, microglia will start removing synapses between neurons. While this is a normal part of brain development in a person’s childhood and adolescent years, it can have disastrous effects in the adult brain.

Over the past five years or so, many studies have observed and profiled these varying microglial states but haven’t been able to characterize the genetics behind them. Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated. With that knowledge, they could then flip genes on and off, setting wayward cells back on the right track. Accomplishing that task required surmounting fundamental obstacles that have prevented researchers from controlling gene expression in these cells. For example, microglia are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it. To overcome this, Kampmann’s team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts. The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off – and which Kampmann had a significant hand in developing – with readouts of data that indicate functions and states of individual microglia cells.

Through this analysis, Kampmann and his team pinpointed genes that affect the cell’s ability to survive and proliferate, how actively a cell produces inflammatory substances, and how aggressively a cell prunes synapses. And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.

Source: https://www.ucsf.edu/

Early Alzheimer’s Detection up to 17 Years in Advance

A sensor identifies misfolded protein biomarkers in the blood. This offers a chance to detect Alzheimer’s disease before any symptoms occur. Researchers intend to bring it to market maturity. The dementia disorder Alzheimer’s disease has a symptom-free course of 15 to 20 years before the first clinical symptoms emerge. Using an immuno-infrared sensor developed in Bochum (Germany), a research team is able to identify signs of Alzheimer’s disease in the blood up to 17 years before the first clinical symptoms appear. The sensor detects the misfolding of the protein biomarker amyloid-beta. As the disease progresses, this misfolding causes characteristic deposits in the brain, so-called plaques.

Our goal is to determine the risk of developing Alzheimer’s dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time,” says Professor Klaus Gerwert, founding director of the Centre for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum (RUB). His team cooperated for the study with a group at the German Cancer Research Centre in Heidelberg (DKFZ) headed by Professor Hermann Brenner.

The team published the results obtained with the immuno-infrared sensor in the journal “Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association” on 19 July 2022. This study is supported by a comparative study published in the same journal on 2 March 2022, in which the researchers used complementary single-molecule array (SIMOA) technology.

The researchers analysed blood plasma from participants in the ESTHER study conducted in Saarland for potential Alzheimer’s biomarkers. The blood samples had been taken between 2000 and 2002 and then frozen. At that time, the test participants were between 50 and 75 years old and hadn’t yet been diagnosed with Alzheimer’s disease. For the current study, 68 participants were selected who had been diagnosed with Alzheimer’s disease during the 17-year follow-up and compared with 240 control subjects without such a diagnosis. The team headed by Klaus Gerwert and Hermann Brenner aimed to find out whether signs of Alzheimer’s disease could already be found in the blood samples at the beginning of the study.

The immuno-infrared sensor was able to identify the 68 test subjects who later developed Alzheimer’s disease with a high degree of test accuracy (0,78 AUC, Area under Curve). For comparison, the researchers examined other biomarkers with the complementary, highly sensitive SIMOA technology – specifically the P-tau181 biomarker, which is currently being proposed as a promising biomarker candidate in various studies.

Blood Test Spots Signs of Alzheimer’s Years Before Symptoms Appear

“Unlike in the clinical phase, however, this marker is not suitable for the early symptom-free phase of Alzheimer’s disease,
” as Klaus Gerwert summarises the results of the comparative study. “Surprisingly, we found that the concentration of glial fibre protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor.” Still, by combining amyloid-beta misfolding and GFAP concentration, the researchers were able to further increase the accuracy of the test in the symptom-free stage to 0,83 AUC.

The Bochum researchers hope that an early diagnosis based on the amyloid-beta misfolding could help to apply Alzheimer’s drugs at such an early stage that they have a significantly better effect – for example, the drug Aduhelm, which was recently approved in the USA. “We plan to use the misfolding test to establish a screening method for older people and determine their risk of developing Alzheimer’s dementia,” says Klaus Gerwert. “The vision of our newly founded start-up betaSENSE is that the disease can be stopped in a symptom-free stage before irreversible damage occurs.” Even though the sensor is still in the development phase, the invention has already been patented worldwide. BetaSENSE aims to bring the immuno-infrared sensor to market and have it approved as a diagnostic device so that it can be used in clinical labs.

Source: https://news.rub.de/

Sugary Protein Could Play Key Role In Alzheimer’s Disease

In a bit of “reverse engineering” research using brain tissues from five people who died with Alzheimer’s disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimer’s disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimer’s disease, say the researchers.

Alzheimer’s disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.

Cleaning up the disease-causing forms of amyloid and tau is the job of the brain’s immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimer’s disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.

A sugar molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments, and perhaps prevention of Alzheimer’s disease

Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain,” says Ronald Schnaar, Ph.D., the John Jacob Abel Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study.

Past studies by the researchers showed that for CD33, these “connector” molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.

The study was published online April 20 in the Journal of Biological Chemistry.

Source: https://www.hopkinsmedicine.org/

AI Technology Predicts Alzheimer’s

Fujifilm and the National Center of Neurology and Psychiatry (NCNP) have just released new research which shows that AI technology could help to predict whether or not someone is likely to get Alzheimer’s disease. By monitoring brain activity, Fujifilm and NCNP say that they are able to predict whether a patient with mild cognitive impairment (MCI) will progress to having dementia within two years with an accuracy of up to 88%.

Alzheimer’s disease is the most common cause of dementia and it is estimated that 55 million people worldwide have the neurological condition that causes loss of memory. As the population ages, it’s expected that by 2050, more than 139 million people will suffer from the life-changing condition Using advanced image recognition technology, Fujifilm and NCNP have developed a way in which they are able to monitor the progression of Alzheimer’s from three-dimensional MRI scans of the brain. Deep learning AI technology monitors the hippocampus and the anterior temporal lobe, two areas highly associated with the progression of Alzheimer’s and detects fine atrophy patterns associated with Alzheimer’s.

An MRI scan of the brain showing the progression of Alzheimer’s 

Atrophy is the progressive degeneration or shrinking of muscle or nerve tissues and in relation to dementia, it takes place in the brain. Two types of common atrophy’s are found in patients with MSmuscle atrophy which causes certain muscles to waste away and cerebral atrophy which is a loss of neurons and connections between neurons. The research shows that when AI technology learns an entire brain, it focuses not just on the two areas usually associated with Alzheimer’s but also on the cerebrospinal fluid (a clear colorless fluid found in your brain and spinal cord) and the occipital lobe which is the visual processing area of the brain

By learning to differentiate between areas of the brain that are less relevant to Alzheimer’s, it is much more likely that a highly accurate prediction can be made about the progression of mild cognitive impairment.

Source: https://www.digitalcameraworld.com/

First Trial of Alzheimer’s Nasal Vaccine to Begin

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital. The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center. A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness.

The vaccine uses a substance called Protollin, which stimulates the immune system.

Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines. “The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press release. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells. “The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

Research in this area has paved the way for us to pursue a whole new avenue for potentially treating not only AD, but also other neurodegenerative diseases,” said Tanuja Chitnis, MD, professor of neurology at Brigham and Women’s Hospital and principal investigator of the trial.

I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical are responsible for developing, manufacturing and commercializing Protollin.

Source: https://www.cbsnews.com/