The brain's ability to clear a protein closely linked to Alzheimer's disease is tied to our circadian cycle, according to research published today in PLOS Genetics. The research underscores the importance of healthy sleep habits in preventing the protein Amyloid-Beta 42 (AB42) from forming clumps in the brain, and opens a path to potential Alzheimer's therapies.
"Circadian regulation of immune cells plays a role in the intricate relationship between the circadian clock and Alzheimer's disease," said Jennifer Hurley, an expert in circadian rhythms, and associate professor of biological science at Rensselaer Polytechnic Institute. "This tells us a healthy sleep pattern might be important to alleviate some of the symptoms in Alzheimer's disease, and this beneficial effect might be imparted by an immune cell type called macrophages/microglia."
The research was conducted at the Rensselaer Center for Biotechnology and Interdisciplinary Studies, which has a focus on neurodegenerative disease. Dr. Hurley worked with Rensselaer professors Robert Linhardt, a glycans expert and inventor of synthetic heparin, and Chunyu Wang, whose ongoing research has detailed several mechanisms in the production and spread of proteins implicated in Alzheimer's.
"This insight reveals a new mechanism and path to treatment of neurodegenerative diseases like Alzheimer's through an interdisciplinary approach, and is emblematic of the CBIS strength in research and discovery and provides a new angle to human health and well-being," said Deepak Vashishth, director of the CBIS.
(EurekAlert) A pioneering new study led by (the University College London) UCL and National Institutes of Health (NIH) scientists has revealed, for the first time, why a common genetic variant worsens disease outcomes for people with the devastating adult-onset neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Published in Nature, the study shows how TDP-43 protein depletion, associated with almost all cases (97%) of ALS and half of FTD cases, corrupts the genetic instructions for the critical neuronal protein UNC13A.
Strikingly, it found that a mysterious genetic variant previously associated with disease risk increases the chance of UNC13A’s genetic instructions being corrupted among people with the diseases, thereby worsening risk and severity of ALS and FTD.
UNC13A enables neurons (nerve cells) to communicate with each other via neurotransmitter release, and data from animal models suggests its loss from neurons can be fatal. The researchers believe that the corruption of UNC13A’s genetic instructions in patients may have similarly harmful consequences.
ALS is the most common motor neuron disease and there is no known cure; it affects the brain and spinal cord by attacking the neurons and nerves which control movement, causing them to die. There is currently only one approved drug for ALS in the UK, which extends lifespan by a few months, and is only effective for a tiny minority of patients. One third of patients die within one year of diagnosis.
Neurons in the brain coexist with and rely on many other cell types to function properly. Astrocytes, which take their name from their star shape, ensure the survival of neurons by feeding and detoxifying them with the help of a multifunctional protein, APOE. One of three forms of this protein, APOE4, significantly increases the risk of developing Alzheimer's disease, but the mechanisms at play are unknown. A collaboration between the University of Geneva (UNIGE), the European Molecular Biology Laboratory (EMBL), the University of Zurich and the pharmaceutical company AbbVie has discovered a potential mechanism: far from ceasing to function, APOE4 is on the contrary more efficient. By triggering astrocytic lipid secretion, it causes the accumulation of potentially toxic lipids that are harmful to neurons, and thus might contribute to the development of Alzheimer's disease. These results published in the journal Cell Reports, shed new light on the neurodegenerative mechanisms of a disease that affects nearly 50 million people worldwide.
Astrocytes, present in very large numbers in the brain, have a major protective function. These cells secrete apolipoprotein E (or APOE), a small protein that forms particles containing lipids and vitamins to feed the neurons. It also detoxifies the neurons by getting them rid of "lipid waste" that could become harmful if not removed. As the neurons are unable to eliminate this waste on their own, APOE comes into play to collect it and bring it back to the astrocytes where it is destroyed.
Hearing loss and epilepsy are early features of Parkinson's, according to pioneering new research from Queen Mary University of London—the first UK study of the condition in such a diverse population, published today in JAMA Neurology.
Queen Mary researchers funded by Bart's Charity used electronic primary healthcare records from over a million people living in East London between 1990 and 2018 to explore early symptoms and risk factors for Parkinson's.
The researchers found that known symptoms associated with Parkinson's, including tremor and memory problems, can appear up to ten and five years before diagnosis respectively. They also uncovered two new early features of Parkinson's, epilepsy and hearing loss, and were able to replicate these findings using additional data from the UK Biobank.
Whilst early signs of Parkinson's have been described previously, these studies have largely focused on affluent white populations, with patients from minority ethnic groups and those living in areas of high social deprivation largely under-represented in Parkinson's research to date. The new study provides further evidence of risk factors and early signs of Parkinson's, using data from such a diverse and deprived urban population for the first time.
Researchers have identified amyloid beta (Aβ) detected in blood to originate from peripheral tissues, and that the peptide acts on pancreaticβ-cells to suppress insulin secretion, thereby regulating blood glucose levels. The study, which urges us to be careful when using blood Aβ levels as a diagnostic marker for Alzheimer's disease (AD), was published in the Proceedings of the National Academy of Sciences (PNAS).
"This work was finally published after about 11 years," says Professor Takami Tomiyama of the Department of Translational Neuroscience, Osaka City University Graduate School of Medicine. "It is not only an academic discovery, but also has implications in how we diagnose AD."
Based on what is known, this study sought to explore some unknowns. First, as AD is caused by the accumulation of Aβ in the brain, it is thought that Aβ levels in the blood reflect the pathology in the brain and are currently used as a diagnostic marker. However, Aβ is generated from the amyloid precursor protein (APP) through the function of two enzymes, β- and γ-secretases, and this mechanism is expressed in many of the body's peripheral tissues, not only in the brain, causing the origin of blood Aβ to remain unknown. Second, epidemiological studies have shown type 2 diabetes to be a strong risk factor for the development of AD, yet the mechanism linking these two diseases has eluded researchers as well.
Researchers have identified a link suggesting that lithium could decrease the risk of developing dementia, which affects nearly one million people in the UK.
The researchers, from the University of Cambridge, conducted a retrospective analysis of the health records of nearly 30,000 patients from Cambridgeshire and Peterborough NHS Foundation Trust. The patients were all over the age of 50 and accessed NHS mental health services between 2005 and 2019.
The analysis suggested that patients who received lithium were less likely to develop dementia than those who did not, although the overall number of patients who received lithium was small.
Their findings, reported in the journal PLoS Medicine, support the possibility that lithium could be a preventative treatment for dementia, and could be progressed to large randomized controlled trials.
A research collaboration between scientists at LSU Health New Orleans and the Karolinska Institutet in Sweden has found that applying specialized pro-resolving lipid mediators intranasally arrested memory loss and brain degeneration in an experimental model of Alzheimer's Disease (AD). The results are published in the journal, Communications Biology.
Neuroinflammation is a hallmark of neurodegenerative disorders, including Alzheimer's Disease. Specialized pro-resolving lipid mediators are bioactive compounds composed of fatty acids like omega-3 or their derivatives that resolve inflammation. Neuroprotectin D1 (NPD1), discovered by Nicolas Bazan, MD, Ph.D., Boyd Professor and Director of the LSU Health New Orleans Neuroscience Center of Excellence, and colleagues is one. Previous studies by the Bazan lab demonstrated that NPD1 is protective in experimental stroke as well as retinal damage and that it is in short supply in the memory area of the brains from AD donors.
Resolving inflammation is a complex process involving mediators, cell subtypes and communication pathways. Response includes cell communications that order the activation of protective, pro-survival mechanisms and silence pro-inflammatory signaling pathways. Specialized pro-resolving lipid mediators such as NPD1 are the key signaling molecules in the process.
A Monash University study has found people who live in more affluent areas have superior memories and a lower risk of developing dementia, highlighting the need for better facilities in disadvantaged areas to promote healthy lifestyle habits and help curtail the growing burden of dementia.
The study analyzed data collected between 2016 and 2020 from the longitudinal, population-based Healthy Brain Project from the Turner Institute for Brain and Mental Health incorporating 4,656 participants aged between 40 and 70 years without dementia.
The study found that higher neighborhood-level socioeconomic status (n-SES) was associated with superior memory and lower dementia risk scores.
The findings are now published in JAMA Network Open journal.
With dementia the second leading cause of death among Australians and up to 40 percent of dementia cases potentially preventable, the study identifies that more research, resource and efforts are needed for the lower n-SES to have a preventative impact.
Lead author Associate Professor Matthew Pase says a multi-faceted approach is needed to address some of the results.
The lethargy that many Alzheimer's patients experience is caused not by a lack of sleep, but rather by the degeneration of a type of neuron that keeps us awake, according to a study that also confirms the tau protein is behind that neurodegeneration.
The study's findings contradict the common notion that Alzheimer's patients sleep during the day to make up for a bad night of sleep and point toward potential therapies to help these patients feel more awake.
The data came from study participants who were patients at UC San Francisco's Memory and Aging Center and volunteered to have their sleep monitored with electroencephalogram (EEG) and donate their brains after they died.
Being able to compare sleep data with microscopic views of their post-mortem brain tissue was the key to answering a question that scientists have been pondering for years.
"We were able to prove what our previous research had been pointing to—that in Alzheimer's patients who need to nap all the time, the disease has damaged the neurons that keep them awake," said Grinberg, a neuropathologist who, along with psychiatrist Thomas Neylan, MD, is a senior author on the study, which appears in the April 4, 2022 issue of JAMA Neurology.
Half of Older Adults Now Die With a Dementia Diagnosis, up Sharply From Two Decades Ago
Summary: Almost 50% of older adults now die with a recorded diagnosis of dementia, up 36% from two decades ago.
This is some really bad news. Must be something in the environment is my guess that is causing this effect on the population.
from what I've seen posted by doctors on the topic, it's probably more to do with better diagnostics and people living longer. Which suggests that this may be something that eventually comes for us all, and we've either missed many of the signs in the past or died before enough evidence was present to find it in many people.
which is one of my fears. as we talk a lot about increases of life span and longevity, I've expressed concern that the brains that make us up may not be up to the task of longer term running, and it's not clear to me that we can replace brain matter like we could a heart or living with a rejection proof version of those.
Things wear out. some you can repair or replace, but eventually the question of the part that is you, can wear out.
The complete set of nucleic acid sequences composing chromosomes in humans, encoded as DNA, is known as the "human genome sequence." Neuroscientists predict that approximately 25% of this sequence has a regulatory function, while only 1.5% encodes protein.
In recent years, many epigenetics studies have tried to identify the mechanisms through which regulatory sequences in the human genome activate or inhibit the expression of genes in response to environmental factors. This could in turn help to modify these sequences using genetic techniques, to reduce the prevalence of genetically inherited diseases or conditions.
Researchers at Icahn School of Medicine at Mount Sinai in New York have recently carried out a study specifically examining chromosomal organizations that are associated with the heritability of two major psychiatric conditions, namely schizophrenia and bipolar disorder. Their paper, published in Nature Neuroscience, unveiled a series of alterations liked to the organization of the genome in three-dimensional (3D) space in brains of patients with these two psychiatric disorders, which are known to have a similar genetic risk architecture.
People who are organized, with high levels of self-discipline, may be less likely to develop mild cognitive impairment as they age, while people who are moody or emotionally unstable are more likely to experience cognitive decline late in life, according to research published by the American Psychological Association.
The research, published in the Journal of Personality and Social Psychology, focused on the role three of the so-called "Big Five" personality traits (conscientiousness, neuroticism and extraversion) play in cognitive functioning later in life.
"Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan," said lead author Tomiko Yoneda, Ph.D., of the University of Victoria. "The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes."
Researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) today reported the discovery of a novel mechanism by which pathological forms of tau protein cause neurons to die. Alzheimer's disease and chronic traumatic encephalopathy (CTE) are among more than 20 disorders that include tau protein pathology.
The newly found mechanism of tau-induced damage can be altered pharmacologically, the scientists noted, making it a novel target for drug development.
The study, published in Alzheimer's & Dementia, "provides a framework for future studies in vertebrate models of tauopathy and eventually clinical trials in people," first author Gabrielle Zuniga said. Zuniga is an MD/Ph.D. student in the South Texas Medical Scientist Training Program offered jointly by the Joe R. and Teresa Lozano Long School of Medicine and the Graduate School of Biomedical Sciences of UT Health San Antonio.
In its later stages, Parkinson's disease often confines sufferers to a bed or a wheelchair.
People with advanced Parkinson's disease often struggle to walk more than a few steps or sleep through the night, but new research offers hope of relief from these two debilitating symptoms.
Suffered by millions worldwide, the degenerative disease erodes motor functions and in its later stages often confines patients to a bed or wheelchair.
This is due to a condition called orthostatic hypotension, which occurs when a person stands up and their blood pressure drops, causing dizziness and even fainting after a couple of steps.
For Parkinson's sufferers, it happens because a regulator in the brain—which normally ensures sufficient blood flows to the brain when we stand up—has been disrupted.
But new French research published in the New England Journal of Medicine last week found that a spinal cord implant could help advanced Parkinson's patients get back on their feet.
Drug-induced parkinsonism is not well understood. Chronic use of flunarizine (FNZ), a drug often used for treating dizziness, migraine, epilepsy, and peripheral vascular diseases, may induce parkinsonism. Previous investigations point out that the disruption of mitochondrial quality control, essential for mitochondrial homeostasis and function, degrades brain functions, and is causally related to parkinsonism disease. Still, there is limited knowledge about the exact mechanism of drug-induced parkinsonism, which hinders the development of prevention and treatment.
Recently, researchers from Guangzhou Institutes of Biomedicine and Health (GIBH) of the Chinese Academy of Sciences (CAS) and the Second Affiliated Hospital of Zhejiang University School of Medicine have revealed the mechanisms of FNZ-inducing parkinsonism by provoking the integration of mitochondria and lysosomes, named as mitolysosome, and causing mitochondrial reduction in brains. This study was published in Science Advances.
The researchers noticed that mice treated with FNZ showed parkinsonism-like symptoms in the rotarod test, the open-field test and Morris water maze test, including decreased coordination and balance and decreased ability to learn and to memorize.
The team detected an increase in glucose uptake in the brains of FNZ-treated mice by [18F]-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scanning, and significant reductions of mitochondrial proteins specifically in brains, but not in other tissues.
Parkinson's disease is perhaps best known for its movement-related symptoms, particularly tremors and stiffness.
But the disease is also known to hinder vocal production, giving those with Parkinson's a soft monotonous voice. Those symptoms, research has suggested, often appear much earlier in the disease's development—sometimes decades before movement-related symptoms.
New research by University of Arizona neuroscientists suggests that a specific gene commonly associated with Parkinson's may be behind those vocal-related issues—a finding that could help lead to earlier diagnoses and treatments for Parkinson's patients.
Working with rats, neuroscientists at Johns Hopkins University have pinpointed a mechanism in the brain responsible for a common type of age-related memory loss. The work, published today in Current Biology, sheds light on the workings of aging brains and may deepen our understanding of Alzheimer's disease and similar disorders in humans.
"We're trying to understand normal memory and why a part of the brain called the hippocampus is so critical for normal memory," said senior author James Knierim, a professor at the university's Zanvyl Krieger Mind/Brain Institute. "But also with many memory disorders, something is going wrong with this area."
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.
The study was published online April 20 in the Journal of Biological Chemistry.
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.
