Category Archives: Research News (General)

Many diseases, including Parkinson’s disease, can be treated with electrical stimulation from an electrode implanted in the brain. However, the electrodes can produce scarring, which diminishes their effectiveness and can necessitate additional surgeries to replace them.

Now, in a study published in Scientific Reports, researchers have demonstrated that making these electrodes much smaller can essentially eliminate this scarring, potentially allowing the devices to remain in the brain for much longer.

Many Parkinson’s patients have benefited from treatment with low-frequency electrical current delivered to a part of the brain involved in movement control. The electrodes used for this deep brain stimulation are a few millimeters in diameter. After being implanted, they gradually generate scar tissue through the constant rubbing of the electrode against the surrounding brain tissue. This process, known as gliosis, contributes to the high failure rate of such devices: About half stop working within the first six months.

Previous studies have suggested that making the implants smaller or softer could reduce the amount of scarring, so the research team set out to measure the effects of both reducing the size of the implants and coating them with a soft polyethylene glycol (PEG) hydrogel.

In mice, the researchers tested both coated and uncoated glass fibers with varying diameters and found that there is a tradeoff between size and softness. Coated fibers produced much less scarring than uncoated fibers of the same diameter. However, as the electrode fibers became smaller, down to about 30 microns (0.03 millimeters) in diameter, the uncoated versions produced less scarring, because the coatings increase the diameter. This suggests that a 30-micron, uncoated fiber is the optimal design for implantable devices in the brain.

The question now is whether fibers that are only 30 microns in diameter can be adapted for electrical stimulation, drug delivery, and recording electrical activity in the brain. Such devices could be potentially useful for treating Parkinson’s disease or other neurological disorders, the researchers say.

Paper: “Making brain implants smaller could prolong their lifespan: Thin fibers could be used to deliver drugs or electrical stimulation, with less damage to the brain.”
Reprinted from materials provided by the Massachusetts Institute of Technology.

In a new study published in Molecular Psychiatry, researchers have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment.

Even in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, the research team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease.

The study included 16 patients at different stages of Alzheimer’s disease. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals. A notable correlation between the size of the deposit and episodic memory impairment was also found, the researchers said, noting that this could explain differences in disease progression across patients.

Paper: “Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia”
Reprinted from materials provided by Karolinska Institutet.

A new article published in JAMA Neurology compares survival rates among patients with synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, Parkinson’s disease dementia and multiple system atrophy with parkinsonism, with individuals in the general population.

The population-based study included all the residents of Minnesota’s Olmsted County and identified 461 patients with synucleinopathies and 452 patients without for comparison.

From 1991 through 2010, the 461 patients with a synucleinopathy diagnosis included 309 with Parkinson’s disease, 81 with dementia with Lewy bodies, 55 with Parkinson’s disease dementia and 16 with multiple system atrophy with parkinsonism. Parkinsonism was defined as the presence of at least 2 of 4 cardinal signs: rest tremor, bradykinesia, rigidity and impaired postural reflexes.

Of the 461 patients with synucleinopathies, 316 (68.6 percent) died during follow-up, while among the 452 participants used for comparison, 220 (48.7 percent) died during follow-up.

Overall, patients with synucleinopathies died about two years earlier than participants without in the comparison group. The highest risk of death was seen among patients with multiple system atrophy with parkinsonism, followed by patients with dementia with Lewy bodies, Parkinson’s disease dementia and Parkinson’s disease, according to the results.

Paper: “Survival and Causes of Death Among People With Clinically Diagnosed Synucleinopathies With Parkinsonism”
Reprinted from materials provided by The JAMA Network.

In a new paper, researchers have demonstrated that measuring neurofilaments provides reliable confirmation of an ALS diagnosis.

Neurofilaments are structural proteins in the cytoskeleton, which are present in high concentrations in motor neurons. It has long been known that the lumbar fluid in ALS patients contains a higher concentration of neurofilaments, perhaps because they are released from sick motor neurons. Now, researchers have carried out detailed research into this phenomenon, which has been published in Neurology.

The scientists say that they have demonstrated that a particular kind of neurofilament (pNfH, phosphorylated neurofilament heavy) can be shown to markedly increase in ALS patients’ lumbar fluid.

The researchers have also demonstrated that there is a good correlation between the degree of neurofilament increase and the extent of the motor neuron loss. This indicates that the test reflects the underlying disease process. Whether the implementation of the test will also lead to a shorter time before diagnosis is currently still being researched.

This diagnostic test represents a significant step forward because valuable time is still lost at present in diagnosing ALS, with diagnosis currently taking an average of one year from the first symptoms. The researchers hope that these tests will allow treatment to be started sooner.

Paper: “Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease”
Reprinted from materials provided by VIB – Flanders Interuniversity Institute for Biotechnology.

A research team has developed a novel measure of disease progression for Huntington’s disease (HD), enabling them to identify a genetic modifier associated with how rapidly the disease progresses.

The study was published in Lancet Neurology.

HD is a fatal neurological disease caused by a genetic mutation. Larger mutations are linked to rapidly progressing disease, but that does not account for all aspects of disease progression.

The research team used the high-quality phenotypic data from the intensively studied TRACK-HD cohort of people with the HD gene mutation. They established that different symptoms of disease progress in parallel, so they were able to combine the data from 24 cognitive, motor and MRI brain imaging variables to generate their progression score for genetic analysis.

They then looked for areas of the genome associated with their progression measure, and found a significant result in their sample of 216 people, which they then validated in a larger sample of 1773 people from a separate cohort, the European Huntington’s Disease Network (EHDN) REGISTRY study.

The genetic signal is likely to be driven by the gene MSH3, a DNA repair gene which has been linked to changes in size of the HD mutation. The researchers identified that a variation in MSH3 encodes an amino acid change in the gene. MSH3 has previously been extensively implicated in the pathogenesis of HD in both mouse and cell studies. The group’s findings may also be relevant to other diseases caused by repeats in the DNA, including some spinocerebellar ataxias.

Paper: “Identification of genetic variants associated with Huntington’s disease progression: a genome-wide association study”
Reprinted from materials provided by University College London.

Researchers have found the first direct evidence that autoimmunity—in which the immune system attacks the body’s own tissues—plays a role in Parkinson’s disease, the neurodegenerative movement disorder. The findings raise the possibility that the death of neurons in Parkinson’s could be prevented by therapies that dampen the immune response.

The study was published in Nature.

Scientists once thought that neurons were protected from autoimmune attacks. However, in a 2014 study, the researchers demonstrated that dopamine neurons (those affected by Parkinson’s disease) are vulnerable because they have proteins on the cell surface that help the immune system recognize foreign substances. As a result, they concluded, T cells had the potential to mistake neurons damaged by Parkinson’s disease for foreign invaders.

The new study found that T cells can be tricked into thinking dopamine neurons are foreign by the buildup of damaged alpha-synuclein proteins, a key feature of Parkinson’s disease.

In the study, the researchers exposed blood samples from 67 Parkinson’s disease patients and 36 age-matched healthy controls to fragments of alpha-synuclein and other proteins found in neurons. They analyzed the samples to determine which, if any, of the protein fragments triggered an immune response. Little immune cell activity was seen in blood samples from the controls. In contrast, T cells in patients’ blood samples, which had been apparently primed to recognize alpha-synuclein from past exposure, showed a strong response to the protein fragments. In particular, the immune response was associated with a common form of a gene found in the immune system, which may explain why many people with Parkinson’s disease carry this gene variant.

The researchers hypothesize that autoimmunity in Parkinson’s disease arises when neurons are no longer able to get rid of abnormal alpha-synuclein. The team is now analyzing these responses in additional patients, and are working to identify the molecular steps that lead to the autoimmune response in animal and cellular models.

Paper: “T cells of Parkinson’s disease patients recognize alpha-synuclein peptides”
Reprinted from materials provided by Columbia University Medical Center.

Scientists have, for the first time, characterized the molecular markers that make the brain’s front lines of immune defense—cells called microglia—unique. In the process, they discovered further evidence that microglia may play roles in a variety of neurodegenerative and psychiatric illnesses, including Alzheimer’s, Parkinson’s and Huntington’s diseases as well as schizophrenia, autism and depression.

Genes that have previously been linked to neurological diseases are turned on at higher levels in microglia compared to other brain cells, the team reported in a study published in Science.

While the link between microglia and a number of disorders has been explored in the past, the new study offers a molecular basis for this connection.

Microglia are notoriously hard to study. They can’t be easily grown in a culture dish and quickly die outside of a living brain. Setting out to characterize the molecular characteristics of microglia, the researchers collected brain tissue from 19 patients, all of who were having brain surgery for epilepsy, a brain tumor or a stroke. They isolated microglia from areas of tissue that were unaffected by disease, as well as from mouse brains, and then set out to study the cells.

The team used a variety of molecular and biochemical tests to characterize which genes are turned on and off in microglia, how the DNA is marked up by regulatory molecules, and how these patterns change when the cells are cultured. Microglia, they found, have hundreds of genes that are more highly expressed than other types of macrophages, as well as distinct patterns of gene expression compared to other types of brain cells.

Next, the researchers analyzed whether any of the genes that were upregulated in microglia compared to other cells had been previously implicated in disease. Genes linked to a variety of neurodegenerative and psychiatric diseases, they found, were highly expressed in microglia.

For Alzheimer’s, more than half of the genes known to affect a person’s risk of developing the disease were expressed more highly in microglia than other brain cells.

Paper: “An environment-dependent transcriptional network specifies human microglia identity”
Reprinted from materials provided by the Salk Institute.

Researchers have identified two groups of neurons that can be turned on and off to alleviate the movement-related symptoms of Parkinson’s disease. The activation of these cells in the basal ganglia relieves symptoms much longer than current therapies, like deep brain stimulation and pharmaceuticals.

The study was published in the journal Nature Neuroscience.

The study used optogenetics in a mouse model of Parkinson’s to better understand the neural circuitry involved in Parkinson’s disease, and could provide the basis for new experimental treatment protocols.

Parkinson’s disease is caused when the dopamine neurons that feed into the brain’s basal ganglia die and cause the basal ganglia to stop working, preventing the body from initiating voluntary movement.

The basal ganglia is the main clinical target for treating Parkinson’s disease, but currently used therapies do not offer long-term solutions.

To better understand how the neurons in the basal ganglia behave in Parkinson’s, the researchers looked at the inner circuitry of the basal ganglia. They chose to study one of the structures that makes up that region of the brain, a nucleus called the external globus pallidus (GPe). The GPe is known to contribute to suppressing motor pathways in the basal ganglia, but little is known about the individual types of neurons present in the GPe, their role in Parkinson’s disease or their therapeutic potential.

The research group used optogenetics, a technique that turns genetically tagged cells on and off with light. They targeted two cell types in a mouse model for Parkinson’s disease: PV-GPe neurons and Lhx6-GPe neurons. They found that by elevating the activity of PV-GPe neurons over the activity of the Lhx6-GPe neurons, they were able to stop aberrant neuronal behavior in the basal ganglia and restore movement in the mouse model for at least four hours — significantly longer than current treatments.

While optogenetics is used only in animal models, the researchers say their findings could lead to a new, more effective deep brain stimulation protocol.

Paper: “Cell-specific pallidal intervention induces long-lasting motor recovery in dopamine-depleted mice”
Reprinted from materials provided by Carnegie Mellon University.

A new large-scale genetic study found that low body mass index (BMI) is likely not a causal risk factor for Alzheimer’s disease, as earlier research had suggested, according to a study published in the Journal of Clinical Endocrinology & Metabolism.

To examine the association between Alzheimer’s disease and low BMI, the researchers analyzed blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS). Of the participants, 645 individuals developed Alzheimer’s disease.

The researchers analyzed the study participants’ DNA for the presence of five genetic variants that have strong associations with BMI. Based on how many variants were found, participants were divided into four groups to reflect the likelihood of low BMI. The researchers also analyzed data from up to 249,796 individuals participating in the Genetic Investigation of ANthropometric Traits (GIANT) consortium for the genetic variants closely linked to low BMI.

The analysis found the presence of the genetic variants tied to low BMI was not associated with increased risk of Alzheimer’s disease. For comparison, the researchers examined if individuals with genetic variants connected to high BMI were more likely to have type 2 diabetes and did find the expected causal relationship.

Paper: “Body Mass Index and Risk of Alzheimer Disease: a Mendelian Randomization Study of 399,536 Individuals”
Reprinted from materials provided by The Endocrine Society.

A new study published in the journal Scientific Reports shows that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with amyotrophic lateral sclerosis (ALS) by repairing damage to the blood-spinal cord barrier.

The researchers say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS.

Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.

The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported. Because stem cells have the ability to develop into many different cell types in the body, researchers have focused on using stem cells to restore function lost through neurodegenerative disorders or injuries.

Damage to the barrier between the blood circulatory system and the central nervous system has been recently recognized as a factor in ALS development, leading researchers to work on targeting the barrier for repair as a potential strategy for ALS therapy.

In this study, the ALS mice were given intravenous treatments of one of three different doses of the bone marrow stem cells. Four weeks after treatment, the scientists determined improved motor function and enhanced motor neuron survival. The mice receiving the higher doses of stem cells fared better in the study.

The transplanted stem cells had differentiated into endothelial cells – which form the inner lining of a blood vessel, providing a barrier between blood and spinal cord tissue — and attached to capillaries in the spinal cord. Furthermore, the researchers observed reductions in activated glial cells, which contribute to inflammatory processes in ALS.

Paper: “Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair”
Reprinted from materials provided by USF Health.