A new MIT study finds that Alzheimer's disease disrupts at least one form of visual memory by degrading a newly identified circuit that connects the vision processing centers of each brain hemisphere.
The results of the study, published in Neuron by a research team based at The Picower Institute for Learning and Memory, come from experiments in mice, but provide a physiological and mechanistic basis for prior observations in human patients: the degree of diminished brain rhythm synchrony between counterpart regions in each hemisphere correlates with the clinical severity of dementia.
"We demonstrate that there is a functional circuit that can explain this phenomenon," said lead author Chinnakkaruppan Adaikkan, a former Picower Institute postdoc who is now an assistant professor in the Center for Brain Research at the Indian Institute of Science (IISc) in Bangalore. "In a way we uncovered a fundamental biology that was not known before."
Specifically, Adaikkan's work identified neurons that connect the primary visual cortex (V1) of each hemisphere and showed that when the cells are disrupted, either by genetic alterations that model Alzheimer's disease or by direct laboratory perturbations, brain rhythm synchrony becomes reduced and mice become significantly less able to notice when a new pattern appeared on a wall in their enclosures. Such recognition of novelty, which requires visual memory of what was there the prior day, is an ability commonly disrupted in Alzheimer's.
A lipid found in the membranes of neurons may play a fundamental role in the development and progression of Alzheimer's disease, according to a study by Penn State College of Medicine researchers. Their findings, published in ACS Chemical Neuroscience, provide possibilities for new approaches to pharmaceutical research on Alzheimer's disease.
Alzheimer's disease is a common neurodegenerative disorder, responsible for 60% to 70% of dementia cases. The economic burden associated with caring for nearly 50 million people worldwide with the condition is annually estimated to be in the hundreds of billions of dollars. Researchers are seeking to better understand how the disease forms and progresses so new therapeutics can be developed for treatment.
A research team led by Nikolay Dokholyan, G. Thomas Passananti Professor and vice chair for research in the Department of Pharmacology, investigated how monosialotetrahexosylganglioside (GM1)—a molecule found in cell membranes—contributes to the formation of toxic oligomers, or harmful protein clusters, consisting of a protein called amyloid beta (Aβ). This protein aggregation has been associated with the development and progression of Alzheimer's disease.
Parkinson's disease is notoriously difficult to diagnose as it relies primarily on the appearance of motor symptoms such as tremors, stiffness, and slowness, but these symptoms often appear several years after the disease onset. Now, Dina Katabi, the Thuan (1990) and Nicole Pham Professor in the Department of Electrical Engineering and Computer Science (EECS) at MIT and principal investigator at MIT Jameel Clinic, and her team have developed an artificial intelligence model that can detect Parkinson's just from reading a person's breathing patterns.
The tool in question is a neural network, a series of connected algorithms that mimic the way a human brain works, capable of assessing whether someone has Parkinson's from their nocturnal breathing—i.e., breathing patterns that occur while sleeping. The neural network, which was trained by MIT Ph.D. student Yuzhe Yang and postdoc Yuan Yuan, is also able to discern the severity of someone's Parkinson's disease and track the progression of their disease over time.
Yang and Yuan are co-first authors on a new paper describing the work, published today in Nature Medicine. Katabi, who is also an affiliate of the MIT Computer Science and Artificial Intelligence Laboratory and director of the Center for Wireless Networks and Mobile Computing, is the senior author. They are joined by 12 colleagues from Rutgers University, the University of Rochester Medical Center, the Mayo Clinic, Massachusetts General Hospital, and the Boston University College of Health and Rehabilition.
If you're a senior who struggles to remember where you put your car keys, could noninvasive brain stimulation boost your memory?
Yes, claims a new study that found folks who were treated with transcranial alternating current stimulation for four days in a row showed greater improvements in their ability to recall things than people who underwent a sham procedure. The effect seemed to last for weeks.
"The effects were moderate to large, and an overwhelming majority of people experienced the memory improvements," study author Robert Reinhart said during a recent media briefing on the findings. Reinhart is the director of the Cognitive & Clinical Neuroscience Laboratory at Boston University.
For the study, 150 adults aged 65 to 88 received treatment targeting their short-term memory, long-term memory, or a placebo procedure. Most were experiencing normal age-related declines in memory. No one in the study had been diagnosed with Alzheimer's disease.
Participants in the active treatment groups wore a shower cap with embedded electrodes that was hooked up to a brain stimulation device that emits weak electrical currents via the electrodes. Each session lasted 20 minutes, and folks were asked to listen to and then immediately recall five lists of 20 words during treatment.
A study that assessed the brains of 99 World Trade Center (WTC) responders by using diffusion tractography, a 3D imaging technique, showed that WTC responders with cognitive impairment (CI), a possible sign of dementia, and post-traumatic stress disorder (PTSD), have a different presentation of the white matter in their brains compared to responders with CI without PTSD. Led by researchers at Stony Brook University affiliated with the Stony Brook WTC Health and Wellness Program, the study suggests a specific form of dementia could be affecting WTC responders who also have PTSD. The findings are published early online in the Journal of Alzheimer's Disease.
According to the authors, this is the first study to examine white matter alterations using connectometry in a sample of WTC responders in mid-life (average age: 56) with and without concurrent PTSD. The goal of the study was to examine and elucidate the extent to which white matter tract integrity might be impaired in WTC responders with CI and/or PTSD. Previously, the researchers had identified changes in white matter diffusivity in small numbers of responder patients.
"Our findings are by no means conclusive in terms of defining CI or dementia in WTC responders, and if this study provides evidence of a new form of dementia emerging," says Sean Clouston, Ph.D., lead author and Associate Professor in the Program in Public Health, and in the Department of Family, Population, and Preventive Medicine at Stony Brook University.
Researchers uncover where and why proteins malfunction in Parkinson's disease
by The Francis Crick Institute
Scientists at the Francis Crick Institute, UCL and the University of Edinburgh have uncovered how a build-up of harmful protein starts to happen within neurons in Parkinson's disease, ultimately causing nerve cell death. By looking at how, where and why this build-up happens, the work provides unique insight into a key biological process driving Parkinson's.
Parkinson's is a progressive neurodegenerative disease that causes tremors, slowing of movements, stiffness and can progress to cause severe cognitive problems. It affects around 145,000 people in the UK, with this number expected to increase as more people live longer.
Parkinson's is caused by a loss of neurons in specific parts of the brain. In affected nerve cells, a protein called alpha-synuclein misfolds and clumps together into harmful structures. The mechanisms behind this are not yet fully understood.
In their paper, published in Nature Neuroscience today, the researchers developed a new sensitive approach to study what happens to alpha-synuclein during the earliest stages of disease.
Huntington's disease—a hereditary and fatal genetic disorder—has long been considered a neuronal disease due to the permanent loss of medium spiny motor neurons, the death of which over time is responsible for the clinical hallmarks of the disease: involuntary movements, problems with coordination, cognitive decline, depression, and psychosis.
However, a growing body of research, including a new study appearing in the journal Cell Reports, suggests that the disease may also flow from defects in glia, important support cells found in the brain. The new study expands our understanding of the underlying mechanisms of the disease, and reinforces the potential of therapies that target glia cells.
Using a novel 3D imaging technology, researchers at Karolinska Institutet, among others, have been able to comprehensively characterize a part of the brain that shows perhaps the earliest accumulation of tau protein, an important biomarker for the development of Alzheimer's disease. The results, published in the journal Acta Neuropathologica, may make it possible in the future to have a more precise neuropathological diagnosis of the Alzheimer's disease spectrum at a very early stage.
Intracellular accumulation of pathological tau protein in the brain is a hallmark of several age-related neurodegenerative disorders, including Alzheimer's disease, which accounts for 60–80% of all dementia cases worldwide.
In a new study, researchers at Karolinska Institutet, SciLifeLab in Stockholm and several universities from Hungary, Canada, Germany and France applied a state-of-the-art volume immuno-imaging technology, in combination with light sheet microscopy, to investigate a human brainstem nucleus called locus coeruleus, which is a key hub in the mammalian brain.
A newly developed agonistic antibody reduced the amyloid pathology in mice with Alzheimer's disease, signaling its promise as a potential treatment for the disease, according to a team of researchers at UTHealth Houston.
Research led by senior author Zhiqiang An, Ph.D., professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth Houston, found that a tetra-variable domain antibody targeting the triggering receptor expressed on myeloid 2 (TREM2)—dubbed TREM2 TVD-lg—reduced amyloid burden, eased neuron damage, and alleviated cognitive decline in mice with Alzheimer's disease. The study was published today in Science Translational Medicine.
"Antibody-based therapy is a viable drug modality for the treatment of Alzheimer's disease," said An, director of the Texas Therapeutics Institute with The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). "One of the major areas of focus at the Texas Therapeutics Institute is developing technologies to deliver antibody-based therapies across the blood-brain barrier for potential treatment of the disease."
TREM2 is a single-pass receptor expressed by microglia—supportive cells that function as scavengers in the central nervous system. Microglia play a crucial role in the removal of amyloids that cluster around amyloid-beta plaques, a hallmark of Alzheimer's disease.
While previous research has shown that TREM2 plays an important role in the pathophysiology of Alzheimer's disease, the recent findings suggest that increasing TREM2 activation could have therapeutic effects such as improved cognition.
A new method to detect Parkinson's disease has been determined by analyzing sebum with mass spectrometry.
The study, published today in the JACS Au , have found that there are lipids of high molecular weight that are substantially more active in people suffering from Parkinson's disease.
The researchers from The University of Manchester used cotton swabs to sample people and identify the compounds present with mass spectrometry. The method developed involves paper spray ionization mass spectrometry combined with ion mobility separation and can be performed in as little as three minutes from swab to results.
Professor Perdita Barran at The University of Manchester, who led the research said, "We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson's Disease that could be used in clinic."
The research used a sample group of 79 people with Parkinson's compared with a heathy control group of 71 people.
The study has arisen from the observation of Joy Milne, who discovered that she can distinguish PD in individuals from a distinct body odor before clinical symptoms occur.
Joy has hereditary Hyperosmia—a heightened sensitivity to smells—which has been exploited to find that Parkinson's has a distinct odor which is strongest where sebum collects on patient's backs and is less often washed away.
One of the most upsetting aspects of age-related memory decline is not being able to remember the face that accompanies the name of a person you just talked with hours earlier. While researchers don't understand why this dysfunction occurs, a new study conducted at University of Maryland School of Medicine (UMSOM) has provided some important new clues. The study was published on September 8 in Aging Cell.
Using aging mice, researchers have identified a new mechanism in neurons that causes memories associated with these social interactions to decline with age. In addition, they were able to reverse this memory loss in the lab.
The researchers report that their findings identified a specific target in the brain that may one day be used to develop therapies that could prevent or reverse memory loss due to typical aging. Aging memory problems are distinct from those caused by diseases like Alzheimer's or dementia. At this time, there are no medications that can prevent or reverse cognitive decline due to typical aging.
"If an older adult attends a cocktail party, afterwards they would most likely recognize the names or the faces of the other attendees, but they might struggle with remembering which name went with which face," said the study leader Michy Kelly, Ph.D., Associate Professor of Anatomy and Neurobiology at UMSOM.
Researchers from Johns Hopkins Medicine and the Dana Farber Cancer Institute in Boston have shown that a hormone secreted into the blood during endurance, or aerobic, exercise reduces levels of a protein linked to Parkinson's disease and halts movement problems in mice.
Parkinson's disease, a neurologic condition that causes people to lose control over their muscles and movements, affects about 1 million people in the U.S.
If confirmed in additional laboratory research and clinical trials, the researchers' study in mice engineered to have Parkinson's disease symptoms could pave the way for a Parkinson's disease therapy based on the hormone irisin.
Results of the researchers' tests appeared Aug. 31 in Proceedings of the National Academy of Sciences.
Infections treated with specialty hospital care in early- and mid-life are associated with an increased subsequent risk of Alzheimer's (AD) and Parkinson's diseases (PD), but not amyotrophic lateral sclerosis (ALS), according to a new study publishing September 15 in the open-access journal PLOS Medicine by Jiangwei Sun of Karolinska Institute, Sweden, and colleagues.
Experimental studies in animals have suggested that infection plays a role in the development of some neurodegenerative diseases, but supporting evidence in humans is limited. In the new study, researchers used data on people diagnosed with AD, PD or ALS from 1970–2016 in Sweden, as well as five matched controls per case, all identified from the Swedish National Patient Register. The analysis included 291,941 AD cases, 103,919 PD cases and 10,161 ALS cases.
A hospital-treated infection five or more years before diagnosis was associated with a 16% higher risk of AD (95%CI: 1.15–1.18, P < 0.001) and a 4% higher risk of PD (95%CI: 1.02–1.06, P < 0.001), with similar risks seen for bacterial, viral and other infections and for different sites of infection. The highest risk of disease was seen in people with multiple hospital-treated infections before the age of 40, with more than double the risk of AD (OR=2.62, 95%CI: 2.52–2.72, P < 0.001) and more than 40% increase in the risk of PD (OR=1.41, 95%CI: 1.29–1.53, 3 44 P < 0.001). No association was observed for ALS, regardless of age at diagnosis.
Parkinson's disease is the fastest-growing neurodegenerative disease, now affecting more than 10 million people worldwide, yet clinicians still face huge challenges in tracking its severity and progression.
Clinicians typically evaluate patients by testing their motor skills and cognitive functions during clinic visits. These semisubjective measurements are often skewed by outside factors—perhaps a patient is tired after a long drive to the hospital. More than 40 percent of individuals with Parkinson's are never treated by a neurologist or Parkinson's specialist, often because they live too far from an urban center or have difficulty traveling.
In an effort to address these problems, researchers from MIT and elsewhere demonstrated an in-home device that can monitor a patient's movement and gait speed, which can be used to evaluate Parkinson's severity, the progression of the disease, and the patient's response to medication.
For decades, researchers from all over the world have been working hard to understand Alzheimer's disease. Now, a collaboration between the Department of Biomedicine and the Department of Clinical Medicine at Aarhus University has resulted in a flock of minipigs that could lead to a major step forward in the research and treatment of Alzheimer's.
The cloned pigs were born with a mutation in the gene SORL1, which is interesting because the mutations are found in up to 2-3% of all early onset Alzheimer's cases in human beings.
Due to the gene mutation, the pigs develop signs of Alzheimer's at a young age. This gives the researchers an opportunity to follow the early signs of the disease, as the pigs show changes in the same biomarkers that are used to make the diagnosis in humans.
"By following the changes over time in the pigs, we can better understand the earliest changes in the cells. Later, these changes lead to the irreversible alterations in the brain that are the cause of dementia. But now we can follow the pigs before they lose their memory, change their behavior, etc., which will make it possible to test new drugs that can be used at an early stage to prevent SORL1-associated Alzheimer's disease," says Associate Professor Olav Michael Andersen, who is the first author of the study, which has just been published in the scientific journal Cell Reports Medicine.
Alzheimer's disease is a neurodegenerative condition that damages a person's ability to think, remember, and perform basic functions. According to the National Institutes of Health, Alzheimer's affects more than 6 million Americans, mostly ages 65 and older. Though the neurological damage from the disease is irreversible, early detection and intervention has been shown to slow its progression.
Before the onset of Alzheimer's physical symptoms, the most commonly used method to measure an individual's risk of developing the disease is through measuring levels of certain proteins, such as amyloid beta and tau proteins, in spinal fluid. This test is invasive, painful, and expensive.
Now, a team from Caltech and the Huntington Medical Research Institutes has made progress toward developing a simple behavioral test to measure an individual's risk of developing Alzheimer's before any symptoms arise. A paper describing the team's findings appears in the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring on September 20.
Alzheimer's drug shows promise in early results of study
Source: AP
By TOM MURPHY
Shares of Biogen and other drugmakers researching Alzheimer’s disease soared early Wednesday after Japan’s Eisai Co. said its potential treatment appeared to slow the fatal disease’s progress in a late-stage study.
Eisai announced results late Tuesday from a global study of nearly 1,800 people with early-stage Alzheimer’s.
The drugmaker said early results showed that its treatment, lecanemab, reduced patient clinical decline by 27% when compared to a placebo or fake drug after 18 months of the infused treatment. Patients were monitored using a scale that measures how they do in areas like memory, judgement, problem solving and personal care.
Eisai Co. Ltd. said it would discuss full results from the research at a conference in late November. It also plans to publish its findings in a peer-reviewed medical journal.
New research from the University of Cincinnati bolsters a hypothesis that Alzheimer's disease is caused by a decline in levels of a specific protein, contrary to a prevailing theory that has been recently called into question.
UC researchers led by Alberto Espay, MD, and Andrea Sturchio, MD, in collaboration with the Karolinska Institute in Sweden, published the research on Oct. 4 in the Journal of Alzheimer's Disease.
Questioning the dominant hypothesis
The research is focused on a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, meaning dissolvable in water, but it sometimes hardens into clumps, known as amyloid plaques.
The conventional wisdom in the field of Alzheimer's research for more than 100 years stated that Alzheimer's was caused by the buildup of amyloid plaques in the brain. But Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic or infectious stress, transforms into the abnormal amyloid plaques.
Trial results of a drug appearing to slow Alzheimer's disease represent a "historic moment", experts say.
Pharmaceutical companies Eisai and Biogen have said their drug works when given in the early stages of the disease.
The full details have yet to published, but it appears to slow the pace of the brain's decline.
And even the limited data has generated excitement among dementia scientists and charities.
Mental agility
The drug, lecanemab, is designed to remove clumps of toxic beta-amyloid proteins that build up in the brains of people with Alzheimer's disease.
Dozens of other drug trials have failed, leading to questions about whether amyloid was really causing the disease.
In this trial, 1,795 volunteers in the early stages of Alzheimer's disease were injected with lecanemab every two weeks and regularly had their memory and mental agility tested.
The pace of cognitive decline had been reduced by 27% over the course of the 18-month trial, compared with people given a dummy, or placebo, treatment, the pharmaceutical companies said.
They also showed levels of the toxic protein were lowered in the brain.
Side-effects included brain swelling and headaches.
The drug will not work for other forms of dementia.
