By the time people with Alzheimer's disease start exhibiting difficulty remembering and thinking, the disease has been developing in their brains for two decades or more, and their brain tissue already has sustained damage. As the disease progresses, the damage accumulates, and their symptoms worsen.
Researchers at Washington University School of Medicine in St. Louis have found that high levels of a normal protein associated with reduced heart disease also protect against Alzheimer's-like brain damage—at least in mice. The findings, published June 21 in Neuron, suggest that raising levels of the protein—known as low-density lipoprotein receptor (LDL receptor)—could potentially be a way to slow or stop cognitive decline.
Last edited by weatheriscool on Tue Apr 11, 2023 4:35 am, edited 2 times in total.
An investigational Alzheimer's drug reduced molecular markers of disease and curbed neurodegeneration in the brain, without demonstrating evidence of cognitive benefit, in a phase 2/3 clinical trial led by researchers at Washington University School of Medicine in St. Louis through its Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU). These results led the trial leaders to offer the drug, known as gantenerumab, to participants as part of an exploratory open-label extension. The researchers continue to monitor changes in measures of Alzheimer's disease in those participants who are receiving the drug.
The DIAN-TU study (ClinicalTrials.gov Identifier: NCT01760005), published June 21 in Nature Medicine, evaluated the effects of two investigational drugs—gantenerumab, made by Roche and its U.S. affiliate, Genentech, and solanezumab, made by Eli Lilly and Co.—in people with a rare, inherited, early-onset form of Alzheimer's known as dominantly inherited Alzheimer's disease or autosomal dominant Alzheimer's disease. Such people are born with a mutation that causes Alzheimer's, and experience declines in memory and thinking skills starting as early as their 30s or 40s.
Alzheimer's disease is predominant in elderly people, but the way age-related changes to lipid composition affect the regulation of biological processes is still not well understood. Links between lipid imbalance and disease have been established, in which lipid changes increase the formation of amyloid plaques, a hallmark of Alzheimer's disease.
This imbalance inspired researchers from Aarhus University in Denmark to explore the role of lipids comprising the cellular membranes of brain cells.
In Biointerphases, the researchers report on the significant role lipids may play in regulating C99, a protein within the amyloid pathway, and disease progression. Lipids have been mostly overlooked from a therapeutic standpoint, likely because their influence in biological function is not yet fully understood.
Nanosized molecules of a particular chemical element can inhibit the formation of plaque in the brain tissues. This new discovery by researchers at Umeå University, Sweden, in collaboration with researchers in Croatia and Lithuania, provides renewed hope for novel treatments of, for instance, Alzheimer's and Parkinson's disease in the long run.
"This is indeed a very important step that may form the basis of new and efficient treatments of neurodegenerative diseases in the future," says Professor Ludmilla Morozova-Roche at Umeå University.
When proteins misfold they form insoluble fibrils called amyloids, which are involved in several serious diseases such as Alzheimer's and Parkinson's, Corino de Andrade's and the mad cow disease. Amyloid aggregates kill neuronal cells and form amyloid plaques in the brain tissues.
What researchers in Umeå in Sweden, Vilnius in Lithuania and Rijeka in Croatia have discovered is that a particular nanosized molecules can hinder the amyloid formation of pro-inflammatory protein S100A9. These molecules are able even to dissolve already pre-formed amyloids, which has been shown by using atomic force microscopy and fluorescence techniques. The molecules in question are nanosized polyoxoniobates, which is so-called polyoxometalate ions with a negative charge containing the chemical element niobium.
It's a favorite first-order for the day, but while a quick coffee may perk us up, new research from the University of South Australia shows that too much could be dragging us down, especially when it comes to brain health.
In the largest study of its kind, researchers have found that high coffee consumption is associated with smaller total brain volumes and an increased risk of dementia.
Conducted at UniSA's Australian Centre for Precision Health at SAHMRI and a team of international researchers, the study assessed the effects of coffee on the brain among 17,702 UK Biobank participants (aged 37-73), finding that those who drank more than six cups of coffee a day had a 53 per cent increased risk of dementia.
For decades, a key brain area called the mesencephalic locomotor region has been thought to merely regulate locomotion. Now, researchers in Silvia Arber's group have shown that the region is involved in much more than walking, as it contains distinct populations of neurons that control different body movements. The findings could help to improve certain therapies for Parkinson's disease, a neurodegenerative condition that leads to tremor, stiffness, and problems controlling different movements.
Even the mundane act of walking requires complex movements such as postural changes and the coordination of all four limbs. Scientists have known that the mesencephalic locomotor region, which is part of the midbrain, is involved in regulating walking and other forms of locomotion in many animal species. But the function of neurons in this area of the brain remained controversial.
A team co-led by scientists at Scripps Research has used advanced imaging methods to reveal how the production of the Alzheimer's-associated protein amyloid beta (Aβ) in the brain is tightly regulated by cholesterol.
Appearing on line Thursday ahead of print in the Aug. 17 issue of the Proceedings of the National Academy of Sciences (PNAS), the scientists' work advances understanding of how Alzheimer's disease develops and underscores the long-underappreciated role of brain cholesterol. The findings also help explain why genetic studies link Alzheimer's risk to a cholesterol-transporting protein called apolipoprotein E (apoE).
"We showed that cholesterol is acting essentially as a signal in neurons that determines how much Aβ gets made—and thus it should be unsurprising that apoE, which carries the cholesterol to neurons, influences Alzheimer's risk," says study co-senior author Scott Hansen, Ph.D., an associate professor in the Department of Molecular Medicine at Scripps Research, Florida.
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 today in 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."
New research published in Stem Cell Reports has found elevated cholesterol supply from astrocytes to neurons in the model of Alzheimer's disease (AD) brains, suggesting that modulating brain cholesterol could be explored in the search of treatment options for the devastating, degenerative disease.
AD, the most frequent cause of dementia, affects an estimated 24 million people worldwide. With very limited treatment options, scientists are looking for ways to understand the disease better. One hallmark of AD is the emergence of so-called beta-amyloid plaques, clumps of beta-amyloid protein accumulating in the brain and thought to be toxic to adjacent neurons. The causes for Alzheimer's disease and the formation of beta-amyloid plaques are still largely unknown but genetic studies found that a gene called APOE, which is involved in cholesterol metabolism and transport, is linked to AD in the elderly. The APOE gene exists in different versions in people, APOE2, APOE3 and APOE4, but the APO4 gene comes with a relatively higher risk of developing AD.
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.
Researchers from Kaunas universities, 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 percent. The method was developed while analyzing 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 percent of dementia cases. Worldwide, approximately 24 million people are affected, and this number is expected to double every 20 years. Owing to societal aging, 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 Ph.D. student from Nigeria," says Rytis Maskeliūnas, a researcher at the Department of Multimedia Engineering, Faculty of Informatics, Kaunas University of Technology (KTU), Odusami's Ph.D. supervisor.
Progress on treating Alzheimer's disease has been frustratingly slow. A group of scientists in Houston suggest frustration at a very small scale may lead to a new path toward treatment.
Researchers at the University of Houston (UH) and at Rice University, associated with the Rice-based Center for Theoretical Biological Physics (CTBP), found through experiments and computations that amyloid beta peptides, small molecules that are abundant in the brain, go through several intermediate stages of frustration as they "dock and lock" to the tips of growing fibrils.
Folding proteins tend to look for the easiest way to get to their functional forms. Similarly, amyloid beta peptides look for the easiest way to bind to the tips of growing fibrils, but are sometimes held back—or frustrated—when the positive and negative forces between atoms don't immediately align.
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 Australia's second-leading cause of death.
The study, published in the prestigious 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.
"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.
Landmark study presents evidence Alzheimer’s disease begins in the liver
By Rich Haridy
September 15, 2021
https://newatlas.com/science/alzheimers ... -dementia/
An impressive new study is presenting robust evidence showing the toxic proteins thought to be the cause of Alzheimer’s disease may be produced in the liver and travel through the blood before landing in the brain causing neuron damage.
For several decades it has been generally accepted that Alzheimer’s disease is caused by the accumulation of amyloid proteins in the brain. These proteins form toxic aggregations known as plaques and it is these plaques that damage the brain.
Although doubts are growing regarding the veracity of the “amyloid hypothesis,” the build up of these plaques is still the most prominent physiological sign of Alzheimer’s. And one of the more interesting hypotheses going around suggests these damaging amyloid proteins originate in the liver.
The big challenge in investigating this liver-amyloid hypothesis is that amyloid is also produced in the brain. Most mouse models used in Alzheimer’s research involve engineering the animals to overexpress amyloid production in the central nervous system, which only really resembles the minority of humans suffering from hereditary early-onset Alzheimer’s. The vast majority of people developing the disease instead experience what is known as sporadic Alzheimer’s, where the disease develops in older age, with no familial or genetic history.
Researchers at Karolinska Institutet in Sweden have compared how well different Alzheimer's biomarkers predict the progression of the disease and its effect on the memory. They found that early accumulation of tau proteins in the brain as measured by PET scanner was more effective at predicting memory impairment than biomarkers in the cerebrospinal fluid or amyloid plaque in the brain. The results are published in the journal Molecular Psychiatry.
Over 50 million people around the world suffer from dementia. Alzheimer's disease is the most common form of dementia and is characterized by an accumulation of the proteins beta-amyloid (Ab) and tau in the brain, followed by a continuous progression in memory decline. The pathological progression can take different forms and it is difficult to predict how quickly the symptoms will develop in any particular individual. Moreover, the presence of Ab in a person's brain—known as amyloid plaque—does not necessarily mean that the he or she will develop Alzheimer's dementia.
A drug commonly used to treat cancer can restore memory and cognitive function in mice that display symptoms of Alzheimer's disease, new UBC research has found.
The drug, Axitinib, inhibits the growth of new blood vessels in the brain—a feature shared by both cancer tumors and Alzheimer's disease, but this hallmark represents a new target for Alzheimer's therapies.
Mice with Alzheimer's disease that underwent the therapy not only exhibited a reduction in blood vessels and other Alzheimer's markers in their brains, they also performed remarkably well in tests designed to measure learning and memory.
"We are really very excited, because these findings suggest we can repurpose approved anti-cancer drugs for use as treatments for Alzheimer's disease," said Professor Wilf Jefferies, the study's senior author and principal investigator at the Centre for Blood Research, Vancouver Prostate Centre and Michael Smith Laboratories. "It could shorten the clinical development by years."
Alzheimer's disease is estimated to affect 50 million people worldwide. The condition is characterized by cognitive decline, memory loss and dysfunctional changes in the brain.
Cancer drug restores blood-brain barrier to reverse Alzheimer's in mice
By Nick Lavars
October 05, 2021
As researchers continue to search for the causes behind Alzheimer's disease and age-related dementia, one possibility is that a leaky blood-brain barrier could have a role to play, allowing for the easy passage of harmful proteins. A new study has explored how this defense might be shored up through the use of an existing anti-cancer drug, with the authors demonstrating some promising results around the reversal of cognitive decline in mice.
The blood-brain barrier is an almost impenetrable membrane that prevents harmful particles from entering, and is therefore key to maintaining the health of the organ and human body as a whole. One line of thinking when it comes to Alzheimer's disease is that a breakdown in this important barrier can allow proteins and fragments such as tau and beta-amyloid to enter, seeding toxic plaques associated with cognitive decline.
In recent years, studies have shown how these leaks could act as early warning signs for Alzheimer's, and how they allow blood-clotting proteins to enter the brain that cause damage to the synapses. One 2019 study even showed how an anti-inflammatory drug can counter the harmful effects of these invasive proteins and reverse cognitive decline associated with dementia in mice.
For this latest study, scientists at the University of British Columbia looked to build on some of their previous research demonstrating how these problematic leaks in the blood-brain barrier could be the result of proliferating blood vessels. This pointed them toward the idea that an agent that prevents irregular formation of blood vessels could put the brakes on this process, which in turn led them to an already-approved chemotherapy drug called Axitinib.
Researchers at the DZNE and the University Medical Center Göttingen (UMG) have identified molecules in the blood that can indicate impending dementia. Their findings, which are presented in the scientific journal EMBO Molecular Medicine, are based on human studies and laboratory experiments. University hospitals across Germany were also involved in the investigations. The biomarker described by the team led by Prof. André Fischer is based on measuring levels of so-called microRNAs. The technique is not yet suitable for practical use; the scientists therefore aim to develop a simple blood test that can be applied in routine medical care to assess dementia risk. According to the study data, microRNAs could potentially also be targets for dementia therapy.
"When symptoms of dementia manifest, the brain has already been massively damaged. Presently, diagnosis happens far too late to even have a chance for effective treatment. If dementia is detected early, the odds of positively influencing the course of the disease increase," says André Fischer, research group leader and spokesperson at the DZNE site in Göttingen and professor at the Department of Psychiatry and Psychotherapy at UMG. "We need tests that ideally respond before the onset of dementia and reliably estimate the risk of later disease. In other words, tests that give an early warning. We are confident that our current study results pave the way for such tests."
A commonly available oral diuretic pill approved by the U.S. Food and Drug Administration may be a potential candidate for an Alzheimer's disease treatment for those who are at genetic risk, according to findings published in Nature Aging. The research included analysis showing that those who took bumetanide—a commonly used and potent diuretic—had a significantly lower prevalence of Alzheimer's disease compared to those not taking the drug. The study, funded by the National Institute on Aging (NIA), part of the National Institutes of Health, advances a precision medicine approach for individuals at greater risk of the disease because of their genetic makeup.
The research team analyzed information in databases of brain tissue samples and FDA-approved drugs, performed mouse and human cell experiments, and explored human population studies to identify bumetanide as a leading drug candidate that may potentially be repurposed to treat Alzheimer's.
"Though further tests and clinical trials are needed, this research underscores the value of big data-driven tactics combined with more traditional scientific approaches to identify existing FDA-approved drugs as candidates for drug repurposing to treat Alzheimer's disease," said NIA Director Richard J. Hodes, M.D.
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, Ph.D., 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.