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A Genetic Answer to the Alzheimer’s Riddle? What if we could pinpoint a hereditary cause for A

A Genetic Answer to the Alzheimer’s Riddle?

What if we could pinpoint a hereditary cause for Alzheimer’s, and intervene to reduce the risk of the disease? We may be closer to that goal, thanks to a team at the University of Kentucky. Researchers affiliated with the UK Sanders-Brown Center on Aging have completed new work in Alzheimer’s genetics; the research is detailed in a paper published today in the Journal of Neuroscience.

Emerging evidence indicates that, much like in the case of high cholesterol, some Alzheimer’s disease risk is inherited while the remainder is environmental. Family and twin studies suggest that about 70 percent of total Alzheimer’s risk is hereditary.

Recently published studies identified several variations in DNA sequence that each modify Alzheimer’s risk. In their work, the UK researchers investigated how one of these sequence variations may act. They found that a “protective” genetic variation near a gene called CD33 correlated strongly with how the CD33 mRNA was assembled in the human brain. The authors found that a form of CD33 that lacked a critical functional domain correlates with reduced risk of Alzheimers disease. CD33 is thought to inhibit clearance of amyloid beta, a hallmark of Alzheimers disease.

The results obtained by the UK scientists indicate that inhibiting CD33 may reduce Alzheimer’s risk. A drug tested for acute myeloid leukemia targets CD33, suggesting the potential for treatments based on CD33 to mitigate the risk for Alzheimer’s disease. Additional studies must be conducted before this treatment approach could be tested in humans.


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Having a Good Listener Improves Your Brain Health

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.

In the study, published 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.”

An estimated 5 million Americans are living with Alzheimer’s disease, a progressive condition that affects mostly those over 65 and interferes with memory, language, decision-making, and the ability to live independently. Dr. Salinas says that while the disease usually affects an older population, the results of this study indicate that people younger than 65 would benefit from taking stock of their social support. For every unit of decline in brain volume, individuals in their 40s and 50s with low listener availability had a cognitive age that was 4 years older than those with high listener availability.

“These four years can be incredibly precious. Too often we think about how to protect our brain health when we’re much older, after we’ve already lost a lot of time decades before to build and sustain brain-healthy habits,” says Dr. Salinas. “But today, right now, you can ask yourself if you truly have someone available to listen to you in a supportive way, and ask your loved ones the same. Taking that simple action sets the process in motion for you to ultimately have better odds of long-term brain health and the best quality of life you can have.”

Dr. Salinas also recommends that physicians consider adding this question to the standard social history portion of a patient interview: asking patients whether they have access to someone they can count on to listen to them when they need to talk.

“Loneliness is one of the many symptoms of depression, and has other health implications for patients,” says Dr. Salinas. “These kinds of questions about a person’s social relationships and feelings of loneliness can tell you a lot about a patient’s broader social circumstances, their future health, and how they’re really doing outside of the clinic.”

How the Study Was Conducted

Researchers used one of the longest running and most closely monitored community-based cohorts in the U.S., the Framingham Heart Study (FHS), as the source of their study’s 2,171 participants, with an average age of 63. FHS participants self-reported information on the availability of supportive social interactions including listening, good advice, love and affection, sufficient contact with people they’re close with, and emotional support.

Study participants’ cognitive resilience was measured as the relative effect of total cerebral brain volume on global cognition, using MRI scans and neuropsychological assessments taken as part of the FHS. Lower brain volumes tend to associate with lower cognitive function, and in this study, researchers examined the modifying effect of individual forms of social support on the relationship between cerebral volume and cognitive performance.

The cognitive function of individuals with greater availability of one specific form of social support was higher relative to their total cerebral volume. This key form of social support was listener availability and it was highly associated with greater cognitive resilience.

Researchers note that further study of individual social interactions may improve understanding of the biological mechanisms that link psychosocial factors to brain health. “While there is still a lot that we don’t understand about the specific biological pathways between psychosocial factors like listener availability and brain health, this study gives clues about concrete, biological reasons why we should all seek good listeners and become better listeners ourselves,” says Dr. Salinas.

Scientists identify the cause of Alzheimer’s progression in the brain

For the first time, researchers have used human data to quantify the speed of different processes that lead to Alzheimer’s disease and found that it develops in a very different way than previously thought. Their results could have important implications for the development of potential treatments.

The international team, led by the University of Cambridge, found that instead of starting from a single point in the brain and initiating a chain reaction which leads to the death of brain cells, Alzheimer’s disease reaches different regions of the brain early. How quickly the disease kills cells in these regions, through the production of toxic protein clusters, limits how quickly the disease progresses overall.

The researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, who ranged from those with mild cognitive impairment to those with late-stage Alzheimer’s disease, to track the aggregation of tau, one of two key proteins implicated in the condition.

In Alzheimer’s disease, tau and another protein called amyloid-beta build up into tangles and plaques – known collectively as aggregates – causing brain cells to die and the brain to shrink. This results in memory loss, personality changes and difficulty carrying out daily functions.

By combining five different datasets and applying them to the same mathematical model, the researchers observed that the mechanism controlling the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one region to another.

The results, reported in the journal Science Advances, open up new ways of understanding the progress of Alzheimer’s and other neurodegenerative diseases, and new ways that future treatments might be developed.

For many years, the processes within the brain which result in Alzheimer’s disease have been described using terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, since it develops over decades, and a definitive diagnosis can only be given after examining samples of brain tissue after death.

For years, researchers have relied largely on animal models to study the disease. Results from mice suggested that Alzheimer’s disease spreads quickly, as the toxic protein clusters colonise different parts of the brain.

“The thinking had been that Alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain,” said Dr Georg Meisl from Cambridge’s Yusuf Hamied Department of Chemistry, the paper’s first author. “But instead, we found that when Alzheimer’s starts there are already aggregates in multiple regions of the brain, and so trying to stop the spread between regions will do little to slow the disease.”

This is the first time that human data has been used to track which processes control the development of Alzheimer’s disease over time. It was made possible in part by the chemical kinetics approach developed at Cambridge over the last decade which allows the processes of aggregation and spread in the brain to be modelled, as well as advances in PET scanning and improvements in the sensitivity of other brain measurements.

“This research shows the value of working with human data instead of imperfect animal models,” said co-senior author Professor Tuomas Knowles, also from the Department of Chemistry. “It’s exciting to see the progress in this field – fifteen years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”

The researchers found that the replication of tau aggregates is surprisingly slow – taking up to five years. “Neurons are surprisingly good at stopping aggregates from forming, but we need to find ways to make them even better if we’re going to develop an effective treatment,” said co-senior author Professor Sir David Klenerman, from the UK Dementia Research Institute at the University of Cambridge. “It’s fascinating how biology has evolved to stop the aggregation of proteins.”

The researchers say their methodology could be used to help the development of treatments for Alzheimer’s disease, which affects an estimated 44 million people worldwide, by targeting the most important processes that occur when humans develop the disease. In addition, the methodology could be applied to other neurodegenerative diseases, such as Parkinson’s disease.  

“The key discovery is that stopping the replication of aggregates rather than their propagation is going to be more effective at the stages of the disease that we studied,” said Knowles.

The researchers are now planning to look at the earlier processes in the development of the disease, and extend the studies to other diseases such as Frontal temporal dementia, traumatic brain injury and progressive supranuclear palsy where tau aggregates are also formed during disease.

(Image caption: SumaLateral Whole Brain Image. Credit: National Institute of Mental Health, National Institutes of Health, USA)

Breastfeeding may help prevent cognitive decline

A new study led by researchers at UCLA Health has found that women over the age of 50 who had breastfed their babies performed better on cognitive tests compared to women who had never breastfed. The findings, published in Evolution, Medicine and Public Health, suggest that breastfeeding may have a positive impact on postmenopausal women’s cognitive performance and could have long-term benefits for the mother’s brain.

“While many studies have found that breastfeeding improves a child’s long-term health and well-being, our study is one of very few that has looked at the long-term health effects for women who had breastfed their babies,” said Molly Fox, PhD, lead author of the study and an Assistant Professor in the UCLA Department of Anthropology and the Department of Psychiatry and Biobehavioral Sciences. “Our findings, which show superior cognitive performance among women over 50 who had breastfed, suggest that breastfeeding may be ‘neuroprotective’ later in life.”

Cognitive health is critical for wellbeing in aging adults. Yet, when cognition becomes impaired after the age of 50, it can be a strong predictor of Alzheimer’s Disease (AD), the leading form of dementia and cause of disability among the elderly – with women comprising nearly two-thirds of Americans living with the disease.

Many studies also show that phases of a woman’s reproductive life-history, such as menstruation, pregnancy, breastfeeding and menopause can be linked to a higher or lower risk for developing various health conditions like depression or breast cancer, yet few studies have examined breastfeeding and its impact on women’s long-term cognition. Of those that have, there has been conflicting evidence as to whether breastfeeding might be linked to better cognitive performance or Alzheimer’s risk among post-menopausal women.

“What we do know is that there is a positive correlation between breastfeeding and a lower risk of other diseases such as type-2 diabetes and heart disease, and that these conditions are strongly connected to a higher risk for AD,” said Helen Lavretsky, MD, the senior author of the study and a professor in the Department of Psychiatry and Biobehavioral Sciences at the Semel Institute for Neuroscience and Human Behavior at UCLA. 

“Because breastfeeding has also been found to help regulate stress, promote infant bonding and lower the risk of post-partum depression, which suggest acute neurocognitive benefits for the mother, we suspected that it could also be associated with long-term superior cognitive performance for the mother as well,” added Dr. Fox.

To find out, the researchers analyzed data collected from women participating in two cross-sectional randomized controlled 12-week clinical trials at UCLA Health: 1) The “Brain Connectivity and Response to Tai Chi in Geriatric Depression and Cognitive Decline,” included depressed participants. 2) The “Reducing Risk for Alzheimer’s Disease in High-Risk Women through Yoga or Memory Training that included non-depressed participants with some subjective memory complaints and a risk for heart disease.

Among the two trials, 115 women chose to participate, with 64 identified as depressed and 51 non-depressed.  All participants completed a comprehensive battery of psychological tests measuring learning, delayed recall, executive functioning and processing speed. They also answered a questionnaire about their reproductive life-history that included questions about the age they began menstruating, number of complete and incomplete pregnancies, the length of time they breastfed for each child and their age of menopause.

Importantly, none of the participants had been diagnosed with dementia, or other psychiatric diagnoses such as bipolar disorder, alcohol or drug dependence, neurological disorders or had other disabilities preventing their participation or taking any psychoactive medications. There was also no significant difference in age, race, education or other cognitive measures between the depressed and non-depressed participants.

Key findings from the researchers’ analysis of the data collected from questionnaires on the women’s reproductive history revealed that about 65% of non-depressed women reported having breastfed, compared to 44% of the depressed women. All non-depressed participants reported at least one completed pregnancy compared to 57.8% of the depressed participants.

Results from the cognitive tests also revealed that those who had breastfed, regardless of whether they were depressed or not, performed better in all four of the cognitive tests measuring for learning, delayed recall, executive functioning and processing compared to women who had not breastfed.

Separate analyses of the data for the depressed and non-depressed groups also revealed that all four cognitive domain scores were significantly associated with breastfeeding in the women who were not depressed.  But in the women who were depressed, only two of the cognitive domains – executive functioning and processing speed – were significantly associated with breastfeeding. 

Interestingly, the researchers also found that longer time spent breastfeeding was associated with better cognitive performance. When they added up all the time a woman spent breastfeeding in her life, they found that women who did not breastfeed had significantly lower cognitive scores in three out of four domains compared to women who had breastfed for 1-12 months, and in all four domains compared to the women who had breastfed for more than 12 months. Women who had breastfed the longest had the highest cognitive test scores.

“Future studies will be needed to explore the relationship between women’s history of breastfeeding and cognitive performance in larger, more geographically diverse groups of women. It is important to better understand the health implications of breastfeeding for women, given that women today breastfeed less frequently and for shorter time periods than was practiced historically,” said Dr. Fox.

Hit the sleep ‘sweet spot’ to keep brain sharp

Like so many other good things in life, sleep is best in moderation. A multiyear study of older adults found that both short and long sleepers experienced greater cognitive decline than people who slept a moderate amount, even when the effects of early Alzheimer’s disease were taken into account. The study was led by researchers at Washington University School of Medicine in St. Louis.

Poor sleep and Alzheimer’s disease are both associated with cognitive decline, and separating out the effects of each has proven challenging. By tracking cognitive function in a large group of older adults over several years and analyzing it against levels of Alzheimer’s-related proteins and measures of brain activity during sleep, the researchers generated crucial data that help untangle the complicated relationship among sleep, Alzheimer’s and cognitive function. The findings could aid efforts to help keep people’s minds sharp as they age.

The findings were published in the journal Brain.

“It’s been challenging to determine how sleep and different stages of Alzheimer’s disease are related, but that’s what you need to know to start designing interventions,” said first author Brendan Lucey, MD, an associate professor of neurology and director of the Washington University Sleep Medicine Center. “Our study suggests that there is a middle range, or ‘sweet spot,’ for total sleep time where cognitive performance was stable over time. Short and long sleep times were associated with worse cognitive performance, perhaps due to insufficient sleep or poor sleep quality. An unanswered question is if we can intervene to improve sleep, such as increasing sleep time for short sleepers by an hour or so, would that have a positive effect on their cognitive performance so they no longer decline? We need more longitudinal data to answer this question.”

Alzheimer’s is the main cause of cognitive decline in older adults, contributing to about 70% of dementia cases. Poor sleep is a common symptom of the disease and a driving force that can accelerate the disease’s progression. Studies have shown that self-reported short and long sleepers are both more likely to perform poorly on cognitive tests, but such sleep studies typically do not include assessments of Alzheimer’s disease.

To tease apart the separate effects of sleep and Alzheimer’s disease on cognition, Lucey and colleagues turned to volunteers who participate in Alzheimer’s studies through the university’s Charles F. and Joanne Knight Alzheimer Disease Research Center. Such volunteers undergo annual clinical and cognitive assessments, and provide a blood sample to be tested for the high-risk Alzheimer’s genetic variant APOE4. For this study, the participants also provided samples of cerebrospinal fluid to measure levels of Alzheimer’s proteins, and each slept with a tiny electroencephalogram (EEG) monitor strapped to their foreheads for four to six nights to measure brain activity during sleep.

In total, the researchers obtained sleep and Alzheimer’s data on 100 participants whose cognitive function had been monitored for an average of 4 ½ years. Most (88) had no cognitive impairments, 11 were very mildly impaired, and one had mild cognitive impairment. The average age was 75 at the time of the sleep study.

The researchers found a U-shaped relationship between sleep and cognitive decline. Overall, cognitive scores declined for the groups that slept less than 4.5 or more than 6.5 hours per night — as measured by EEG — while scores stayed stable for those in the middle of the range. EEG tends to yield estimates of sleep time that are about an hour shorter than self-reported sleep time, so the findings correspond to 5.5 to 7.5 hours of self-reported sleep, Lucey said.

The U-shaped relationship held true for measures of specific sleep phases, including rapid-eye movement (REM), or dreaming, sleep; and non-REM sleep. Moreover, the relationship held even after adjusting for factors that can affect both sleep and cognition, such as age, sex, levels of Alzheimer’s proteins, and the presence of APOE4.

“It was particularly interesting to see that not only those with short amounts of sleep but also those with long amounts of sleep had more cognitive decline,” said co-senior author David Holtzman, MD, a professor of neurology. “It suggests that sleep quality may be key, as opposed to simply total sleep.”

Each person’s sleep needs are unique, and people who wake up feeling rested on short or long sleep schedules should not feel compelled to change their habits, Lucey said. But those who are not sleeping well should be aware that sleep problems often can be treated.

“I ask many of my patients, ‘How’s your sleep?’” said co-senior author Beau M. Ances, MD, PhD, the Daniel J. Brennan, MD, Professor of Neurology. Ances treats patients with dementia and other neurodegenerative conditions at Barnes-Jewish Hospital. “Often patients report that they’re not sleeping well. Often once their sleep issues are treated, they may have improvements in cognition. Physicians who are seeing patients with cognitive complaints should ask them about their quality of sleep. This is potentially a modifiable factor.”

Our brains have a “fingerprint” too

An EPFL scientist has pinpointed the signs of brain activity that make up our brain fingerprint, which – like our regular fingerprint – is unique.

“I think about it every day and dream about it at night. It’s been my whole life for five years now,” says Enrico Amico, a scientist and SNSF Ambizione Fellow at EPFL’s Medical Image Processing Laboratory and the EPFL Center for Neuroprosthetics. He’s talking about his research on the human brain in general, and on brain fingerprints in particular. He learned that every one of us has a brain “fingerprint” and that this fingerprint constantly changes in time. His findings have just been published in Science Advances.

“My research examines networks and connections within the brain, and especially the links between the different areas, in order to gain greater insight into how things work,” says Amico. “We do this largely using MRI scans, which measure brain activity over a given time period.” His research group processes the scans to generate graphs, represented as colorful matrices, that summarize a subject’s brain activity. This type of modeling technique is known in scientific circles as network neuroscience or brain connectomics. “All the information we need is in these graphs, that are commonly known as “functional brain connectomes”. The connectome is a map of the neural network. They inform us about what subjects were doing during their MRI scan – if they were resting or performing some other tasks, for example. Our connectomes change based on what activity was being carried out and what parts of the brain were being used,” says Amico.

Two scans are all it takes

A few years ago, neuroscientists at Yale University studying these connectomes found that every one of us has a unique brain fingerprint. Comparing the graphs generated from MRI scans of the same subjects taken a few days apart, they were able to correctly match up the two scans of a given subject nearly 95% of the time. In other words, they could accurately identify an individual based on their brain fingerprint. “That’s really impressive because the identification was made using only functional connectomes, which are essentially sets of correlation scores,” says Amico.

(Image caption: Map of functional brain connectomes Credit: © 2021 EPFL)

He decided to take this finding one step further. In previous studies, brain fingerprints were identified using MRI scans that lasted several minutes. But he wondered whether these prints could be identified after just a few seconds, or if there was a specific point in time when they appear – and if so, how long would that moment last? “Until now, neuroscientists have identified brain fingerprints using two MRI scans taken over a fairly long period. But do the fingerprints actually appear after just five seconds, for example, or do they need longer? And what if fingerprints of different brain areas appeared at different moments in time? Nobody knew the answer. So, we tested different time scales to see what would happen,” says Amico.

A brain fingerprint in just 1 minute and 40 seconds

His research group found that seven seconds wasn’t long enough to detect useful data, but that around 1 minute and 40 seconds was. “We realized that the information needed for a brain fingerprint to unfold could be obtained over very short time periods,” says Amico. “There’s no need for an MRI that measures brain activity for five minutes, for example. Shorter time scales could work too.” His study also showed that the fastest brain fingerprints start to appear from the sensory areas of the brain, and particularly the areas related to eye movement, visual perception and visual attention. As time goes by, also frontal cortex regions, the ones associated to more complex cognitive functions, start to reveal unique information to each of us.

The next step will be to compare the brain fingerprints of healthy patients with those suffering from Alzheimer’s disease. “Based on my initial findings, it seems that the features that make a brain fingerprint unique steadily disappear as the disease progresses,” says Amico. “It gets harder to identify people based on their connectomes. It’s as if a person with Alzheimer’s loses his or her brain identity.”

Along this line, potential applications might include early detection of neurological conditions where brain fingerprints get disappear. Amico’s technique can be used in patients affected by autism, or stroke, or even in subjects with drug addictions. “This is just another little step towards understanding what makes our brains unique: the opportunities that this insight might create are limitless.”

Research identifies likely cause of Alzheimer’s disease

The study, published in the prestigious PLOS Biologyjournal 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.

“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.

“Having universities like Curtin working with the pharmaceutical industry is important if we are to tackle this devastating disease,” Mr Harding said.

“In Australia, approximately 250 people are diagnosed with dementia daily, adding to the staggering half a million Australians who are already living with dementia. Without significant medical advances like the breakthrough Professor Mamo’s team has made, it is estimated that the number of Australians living with dementia will exceed one million by 2058. This has a significant impact on families, carers and communities.”

Professor Mamo and his research team’s previous research in this area was awarded the NHMRC-Marshall and Warren Award for the most innovative and potentially transformative research.

Currently, the team is conducting a clinical trial, the Probucol in Alzheimer’s-clinical trial, which is based on previous findings that a historic cardiovascular agent lowers lipoprotein-amyloid production and supports cognitive performance in mice. The mouse models used for this research were developed together with Ozgene.

Cholesterol Drives Alzheimer’s Plaque Formation

Cholesterol manufactured in the brain appears to play a key role in the development of Alzheimer’s disease, new researchindicates.

Scientists from the School of Medicine and their collaborators found that cholesterol produced by cells called astrocytes is required for controlling the production of amyloid beta, a sticky protein that builds up in the brains of patients with Alzheimer’s. The protein accumulates into insoluble plaques that are a hallmark of the disease. Many efforts have targeted these plaques in the hope that removing or preventing them could treat or prevent Alzheimer’s.

The new findings offer important insights into how and why the plaques form and may explain why genes associated with cholesterol have been linked to increased risk for Alzheimer’s. The results also provide scientists with important direction as they seek to prevent Alzheimer’s from developing.

“This study helps us to understand why genes linked to cholesterol are so important to the development of Alzheimer’s disease,” said researcher Heather A. Ferris, MD, PhD, of UVA’s Division of Endocrinology and Metabolism. “Our data point to the importance of focusing on the production of cholesterol in astrocytes and the transport to neurons as a way to reduce amyloid beta and prevent plaques from ever being formed.”

Alzheimer’s Plaques and Cholesterol

While cholesterol is often associated with clogged arteries and heart disease, it plays important roles in the healthy body. The body makes cholesterol naturally so it can produce hormones and carry out other important functions. The new discovery from Ferris and her collaborators adds a new entry to cholesterol’s list of responsibilities.

The work also sheds light on the role of astrocytes in Alzheimer’s disease. Scientists have known that these common brain cells undergo dramatic changes in Alzheimer’s, but they have been uncertain if the cells were suffering from the disease or contributing to it. The new results from Ferris and her collaborators suggest the latter.

The scientists found that astrocytes help drive the progression of Alzheimer’s by making and distributing cholesterol to brain cells called neurons. This cholesterol buildup increases amyloid beta production and, in turn, fuels plaque accumulation.

Normally, cholesterol is kept quite low in neurons, limiting the buildup of amyloid beta. But in Alzheimer’s, the neurons lose their ability to regulate amyloid beta, and the result is plaque formation.

Blocking the astrocytes’ cholesterol manufacturing “robustly” decreased amyloid beta production in lab mice, the researchers report in a new scientific paper. It’s too soon to say if this could be mimicked in people to prevent plaque formation, but the researchers believe that further research is likely to yield important insights that will benefit the battle against Alzheimer’s.

The fact that amyloid beta production is normally tightly controlled suggests that it may play an important role in brain cells, the researchers say. As such, doctors may need to be careful in trying to block or remove amyloid beta. Additional research into the discovery could shed light on how to prevent the over-production of amyloid beta as a strategy against Alzheimer’s, the researchers believe.

“If we can find strategies to prevent astrocytes from over-producing cholesterol, we might make a real impact on the development of Alzheimer’s disease,” Ferris said. “Once people start having memory problems from Alzheimer’s disease, countless neurons have already died. We hope that targeting cholesterol can prevent that death from ever occurring in the first place.”

Algorithm can predict possible Alzheimer’s with nearly 100 per cent accuracy

Researchers from Kaunas universities in Lithuania developed a deep learning-based method that can predict the possible onset of Alzheimer’s disease from brain images with an accuracy of over 99 per cent. The method was developed while analysing functional MRI images obtained from 138 subjects and performed better in terms of accuracy, sensitivity and specificity than previously developed methods.

According to World Health Organisation, Alzheimer’s disease is the most frequent cause of dementia, contributing to up to 70 per cent of dementia cases. Worldwide, approximately 24 million people are affected, and this number is expected to double every 20 years. Owing to societal ageing, the disease will become a costly public health burden in the years to come.

“Medical professionals all over the world attempt to raise awareness of an early Alzheimer’s diagnosis, which provides the affected with a better chance of benefiting from treatment. This was one of the most important issues for choosing a topic for Modupe Odusami, a PhD student from Nigeria”, says Rytis Maskeliūnas, a researcher at the Department of Multimedia Engineering, Faculty of Informatics, Kaunas University of Technology (KTU), Odusami’s PhD supervisor.

Image processing delegated to the machine

One of the possible Alzheimer’s first signs is mild cognitive impairment (MCI), which is the stage between the expected cognitive decline of normal ageing and dementia. Based on the previous research, functional magnetic resonance imaging (fMRI) can be used to identify the regions in the brain which can be associated with the onset of Alzheimer’s disease, according to Maskeliūnas. The earliest stages of MCI often have almost no clear symptoms, but in quite a few cases can be detected by neuroimaging.

However, although theoretically possible, manual analysing of fMRI images attempting to identify the changes associated with Alzheimer’s not only requires specific knowledge but is also time-consuming – application of Deep learning and other AI methods can speed this up by a significant time margin. Finding MCI features does not necessarily mean the presence of illness, as it can also be a symptom of other related diseases, but it is more of an indicator and possible helper to steer toward an evaluation by a medical professional.

“Modern signal processing allows delegating the image processing to the machine, which can complete it faster and accurately enough. Of course, we don’t dare to suggest that a medical professional should ever rely on any algorithm one-hundred-per cent. Think of a machine as a robot capable of doing the most tedious task of sorting the data and searching for features. In this scenario, after the computer algorithm selects potentially affected cases, the specialist can look into them more closely, and at the end, everybody benefits as the diagnosis and the treatment reaches the patient much faster”, says Maskeliūnas, who supervised the team working on the model.

We need to make the most of data

The deep learning-based model was developed as a fruitful collaboration of leading Lithuanian researchers in the Artificial Intelligence sector, using a modification of well-known fine-tuned ResNet 18 (residual neural network) to classify functional MRI images obtained from 138 subjects. The images fell into six different categories: from healthy through the spectre of mild cognitive impairment (MCI) to Alzheimer’s disease. In total, 51,443 and 27,310 images from The Alzheimer’s Disease Neuroimaging Initiative fMRI dataset were selected for training and validation.

The model was able to effectively find the MCI features in the given dataset, achieving the best classification accuracy of 99.99%, 99.95%, and 99.95% for early MCI vs. AD, late MCI vs. AD, and MCI vs. early MCI, respectively.

“Although this was not the first attempt to diagnose the early onset of Alzheimer’s from similar data, our main breakthrough is the accuracy of the algorithm. Obviously, such high numbers are not indicators of true real-life performance, but we’re working with medical institutions to get more data”, says Maskeliūnas.

According to him, the algorithm could be developed into software, which would analyse the collected data from vulnerable groups (those over 65, having a history of brain injury, high blood pressure, etc.) and notify the medical personnel about the anomalies related to the early onset of Alzheimer’s.

“We need to make the most of data”, says Maskeliūnas, “that’s why our research group focuses on the European open science principle, so anyone can use our knowledge and develop it further. I believe that this principle contributes greatly to societal advancement”.

Maskeliūnas, the chief researcher, whose main area focuses on the application of modern methods of artificial intelligence on signal processing and multimodal interfaces, says that the above-described model can be integrated into a more complex system, analysing several different parameters, for example, also monitoring eye movements’ tracking, face reading, voice analysing, etc. Such technology could then be used for self-check and alert to seek professional advice if anything is causing concern.

“Technologies can make medicine more accessible and cheaper. Although they will never (or at least not soon) truly replace the medical professional, technologies can encourage seeking timely diagnosis and help”, says Maskeliūnas.

(Image caption: DAXX (red color at top) prevents the aggregation of mutant p53 protein associated with cancers (dark green color at bottom) in cells).

Restoring “Chaperone” Protein May Prevent Plaque Build-up in Alzheimer’s

For the first time, Penn Medicine researchers showed how restoring levels of the protein DAXX and a large group of similar proteins prevents the misfolding of the rogue proteins known to drive Alzheimer’s and other neurodegenerative diseases, as well as certain mutations that contribute to cancers. The findings could lead to new targeted approaches that would restore a biological system designed to keep key proteins in check and prevent diseases.

The findings were published online in Nature.

The study focuses on DAXX, or death domain-associated protein, which is a member of a large family of human proteins, each with an unusually high content of two specific amino acid residues, aspartate and glutamate, referred to as polyD/E proteins. The various roles of DAXX and approximately 50 other polyD/E proteins in cell processes have emerged over time, but their role as a protein quality control system — a “chaperone” that directs protein folding, so to speak — was unanticipated.

“We solve a decades-long puzzle by showing this group of proteins actually constitute a major protein quality control system in cells and a never-before-seen enabler of proper folding of various proteins — including misfolding-prone proteins associated with various diseases,” said senior author Xiaolu Yang, PhD, a professor of Cancer Biology in the Perelman School of Medicine at the University of Pennsylvania. “Keep that family of proteins functioning properly, and the tangling of rogue proteins may be diminished or stopped altogether.”

Proteins are the workhorses of the cell. To ensure normal cellular function and protect against protein-misfolding associated with disease, organisms have evolved elaborate protein quality control systems to enable efficient protein folding. However, these systems, especially those in humans, are still not well understood, which limits the ability to develop effective therapies.

The researchers showed that DAXX and other polyD/E proteins facilitate the folding of proteins, reverse protein aggregates, and unfold misfolded proteins. They prevent neurodegeneration-associated proteins, such as beta-amyloid and alpha-synuclein from misfolding, tangling, and forming extracellular plaques and intracellular inclusions, they found. Beta-amyloid clumping between the nerve cells is observed in the brains of Alzheimer’s disease patients and the target of many treatment approaches, while intracellular inclusions of alpha-synuclein are observed in the brains of patients with Parkinson’s disease.

The team also showed DAXX’s potential role in treating cancer.

DAXX restores native function to tumor-associated and aggregation-prone p53 proteins, reducing their cancer properties. That’s important because p53 is the preeminent tumor suppressor and mutations in p53 are associated with a bevy of cancers, including lung, colon, pancreatic, ovarian, and breast cancer. Bolstering DAXX function, the authors said, might represent an alternative approach to therapeutically reestablish the tumor suppressive function of mutant p53 to treat patients.

“The findings give us a better understanding of a new biochemical activity that effectively contends with protein misfolding seen in Alzheimer’s and other neurodegenerative diseases, as well as in cancer, and represent an opportunity to develop new approaches to treat these diseases,” Yang said.

Brain Tissue Inflammation Drives Alzheimer’s Disease

Neuroinflammation is the key driver of the spread of pathologically misfolded proteins in the brain and causes cognitive impairment in patients with Alzheimer’s disease, researchers from the University of Pittsburgh School of Medicine reveal in a paper published in Nature Medicine.

(Image caption: The degree of neuroinflammation (red) is more pronounced in brains of patients with Alzheimer’s disease than in healthy individuals. Credit: Adapted from Pascoal et al., Nature Medicine)

For the first time ever, the researchers showed in living patients that neuroinflammation—or activation of the brain’s resident immune cells, called microglial cells—is not merely a consequence of disease progression; rather, it is a key upstream mechanism that is indispensable for disease development.

“As a young resident neurologist in my home country of Brazil, I noticed that many patients with Alzheimer’s disease are left neglected and without access to appropriate care,” said lead author Tharick Pascoal, M.D., Ph.D., assistant professor of psychiatry and neurology at Pitt. “Our research suggests that combination therapy aimed to reduce amyloid plaque formation and limit neuroinflammation might be more effective than addressing each pathology individually.”

Alzheimer’s disease is characterized by the accumulation of amyloid plaques—protein aggregates lodged between nerve cells of the brain—and clumps of disordered protein fibers, called tau tangles, forming inside the nerve cells. Although studies in cultured cells and lab animals amassed ample evidence that microglial activation drives the spread of tau fibers in Alzheimer’s disease, this process has never been proven in humans.

The study findings suggest that targeting neuroinflammation might be beneficial for people with early-stage Alzheimer’s disease and that it might help reverse or at least slow down the accumulation of pathologic tau protein in the brain and stave off dementia.

To determine the mechanism by which disordered tangles of tau protein fibers and amyloid plaques spread across the brain and lead to dementia, the researchers used live imaging to look deep into the brains of people with various stages of Alzheimer’s disease and healthy aging individuals.

The researchers found that neuroinflammation was more prevalent in older people and that it was even more pronounced in patients with mild cognitive impairments and those with Alzheimer’s disease-associated dementia. Bioinformatics analysis confirmed that tau propagation depended on microglial activation—it is a key element that links the effects of amyloid plaque aggregation to tau spread and, ultimately, cognitive impairment and dementia.

“Many elderly people have amyloid plaques in their brains but never progress to developing Alzheimer’s disease,” said Pascoal. “We know that amyloid accumulation on its own is not enough to cause dementia—our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to wide-spread brain damage and cognitive impairment.”

Does Alzheimer’s disease start inside nerve cells?

An experimental study from Lund University in Sweden has revealed that the Alzheimer’s protein amyloid-beta accumulates inside nerve cells, and that the misfolded protein may then spread from cell to cell via nerve fibres. This happens at an earlier stage than the formation of amyloid-beta plaques in the brain, something that is associated with the progression of Alzheimer’s disease.

The study in question builds on previous research based on amyloid-beta’s prion-like properties. This means that the protein adopts a misfolded form that acts as a template for spreading in the brain, where it accumulates and develops plaques.

“The plaques of amyloid-beta outside the nerve cells have long been a target for treatment of Alzheimer’s disease. But as treatments to remove plaque have not helped against dementia, we must develop and investigate other hypotheses in order to find other targets for treatment. Our results indicate that amyloid-beta is highly relevant, but that we must focus on misfolded amyloid-beta inside the nerve cells that arise far earlier than the visible plaques”, says the first author of the study Tomas Roos, doctoral student at Lund University and resident physician at Skåne University Hospital’s neurological clinic.

Amyloid-beta is present in the brain of healthy individuals, but the mechanisms that are disrupted and cause the misfolding remain unclear. The plaques are extracellular, but the results of this study indicate that a misfolding can occur within the cells. Furthermore, the researchers show that there is a continuous exchange of amyloid-beta between the outside and inside of nerve cells, a kind of equilibrium, that is disturbed when misfolded amyloid-beta accumulates both inside and outside nerve cells.

In the study, which was conducted using a mouse model for Alzheimer’s and cell culture, the researchers also noted that misfolded amyloid-beta inside the nerve cells leads to increased amyloid-beta production.

“The increased amyloid-beta caused by misfolded amyloid-beta inside cells can bring about a vicious circle of more and more amyloid-beta production. This could explain the enormous amounts of amyloid-beta that accumulate in the brain of Alzheimer’s patients. First and foremost, the study results are to be replicated in a different Alzheimer’s model. However, our results indicate that many of amyloid-beta’s damaging effects may be caused by what is happening within the cells, independent of plaques. This may explain why so many experimental treatments targeting plaques outside the nerve cells have failed and that we should focus our attention inwards,” concludes Tomas Roos.

As a follow-up to that last answer, here’s a powerful open letter to Will Ferrell by Patti Davis, the daughter of Ronald and Nancy Reagan, who had her own issues with her parents and strongly disagreed with many of her father’s political beliefs. The second paragraph is heartbreaking, no matter who the person lost in the fog of Alzheimer’s or dementia might have once been.

AN OPEN LETTER TO WILL FERRELL

Dear Mr. Ferrell,

I saw the news bulletin — as did everyone — that you intend to portray my father in the throes of Alzheimer’s for a comedy that you are also producing. Perhaps you have managed to retain some ignorance about Alzheimer’s and other versions of dementia. Perhaps if you knew more, you would not find the subject humorous.

Alzheimer’s doesn’t care if you are President of the United States or a dockworker. It steals what is most precious to a human being — memories, connections, the familiar landmarks of a lifetime that we all come to rely on to hold our place secure in this world and keep us linked to those we have come to know and love. I watched as fear invaded my father’s eyes — this man who was never afraid of anything. I heard his voice tremble as he stood in the living room and said, “I don’t know where I am.” I watched helplessly as he reached for memories, for words, that were suddenly out of reach and moving farther away. For ten long years he drifted — past the memories that marked his life, past all that was familiar…and mercifully, finally past the fear.

There was laughter in those years, but there was never humor.

Alzheimer’s is the ultimate pirate, pillaging a person’s life and leaving an empty landscape behind. It sweeps up entire families, forcing everyone to claw their way through overwhelming grief, confusion, helplessness, and anger. Perhaps for your comedy you would like to visit some dementia facilities. I have — I didn’t find anything comedic there, and my hope would be that if you’re a decent human being, you wouldn’t either.

Twice a week I run a support group called Beyond Alzheimer’s for caregivers and family members of those with Alzheimer’s and dementia. I look into haunted eyes that remind me of my own when my father was ill. I listen to stories of helplessness and loss and am continually moved by the bravery of those who wake up every morning not knowing who their loved one will be that day, or what will be lost. The only certainty with Alzheimer’s is that more will be lost and the disease will always win in the end.

Perhaps you would like to explain to them how this disease is suitable material for a comedy.

ucsdhealthsciences: How the Eyes Might Be Windows to the Risk of Alzheimer’s Disease Researchers say

ucsdhealthsciences:

How the Eyes Might Be Windows to the Risk of Alzheimer’s Disease

Researchers say how quickly a person’s pupil dilates while taking cognitive tests  

Alzheimer’s disease (AD) begins to alter and damage the brain years — even decades — before symptoms appear, making early identification of AD risk paramount to slowing its progression.

In a new study published online in the September 9, 2019 issue of the Neurobiology of Aging, scientists at University of California San Diego School of Medicine say that, with further developments, measuring how quickly a person’s pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins.

In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of protein plaques in the brain called amyloid-beta and tangles of a protein called tau. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.

The new study focuses on pupillary responses which are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is the earliest occurring known biomarker for AD; it first appears in the LC; and it is more strongly associated with cognition than amyloid-beta. The study was led by first author William S. Kremen, PhD, and senior author Carol E. Franz, PhD, both professors of psychiatry and co-directors of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine.

The LC drives pupillary response — the changing diameter of the eyes’ pupils — during cognitive tasks. (Pupils get bigger the more difficult the brain task.) In previously published work, the researchers had reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. Critically, in the latest paper, the scientists link pupillary dilation responses with identified AD risk genes.

“Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” said Kremen.


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Yeah. That’s how Alzheimer’s works, right?

Yeah. That’s how Alzheimer’s works, right?


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Though I’ve seen Son Ye-Jin in Crash Landing On You, this film still made me confused if it’s really her I’m watching right now. It’s not that she aged a lot, of course, there’s difference now she’s in her late 30s and getting married sooner to her first love ayieee. She’s an angel that has an immaculate face and voice here. The heart effect they had with her partner to me just made my heart beats go crazy. Melancholy crept into me while I peek at the synopsis. It’s the ignorance that killed me to tears and sadness. Though it’s an open ending for me because I hope that she’ll regain her memory in no time, I still know that it’ll be permanent and lapses may happen always. I’m happy for the heartaches it brought and I’m sad for the little joy it offered me.


A Moment To Remember (2004)

Herbs with the Most Promising Supportive Information for Treating Dementia t the moment, there is noHerbs with the Most Promising Supportive Information for Treating Dementia t the moment, there is no

Herbs with the Most Promising Supportive Information for Treating Dementia

t the moment, there is no cure for dementia. Still, there are few conventional medicines that are known to slow the progression of the disease.

Medicinal herbs intended as a treatment should never replace any conventional medication or therapies and should be regarded as an addition or as a supportive therapy.

A large number of patients in the developing world with dementia, where the use of herbal medicines are often the mainstay of therapy, coupled to a global upswing in the use of natural preparations, underscores the need to fully characterize and understand how medicinal herbs can be used in the management of dementia.

While the effects of these natural remedies are varied, it appears that herbs may be useful in the treatment of dementia in three separate ways:

1. Increasing blood flow to the brain.

2. Decreasing the destruction of neurotransmitters critical to proper brain function.

3. Decreasing the level of agitation known to accompany dementia.

In general, when using medicinal plants as a treatment for any disease, caution should always be a key factor, since herbs can interact with other herbs, medications or supplements.

For more information CLICK HERE:https://www.herbal-supplement-resource.com/dementia-remedies.html
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