Monthly Archives: September 2017

Researchers have identified altered expression of a gene called ANK1, which only recently has been associated with Alzheimer’s disease, in specific cells in the brain.

Researchers studied microglia, astrocytes and neurons in individuals with a pathological diagnosis of Alzheimers using the precise laser capture microdissection technique and compared them to brain samples from healthy individuals and to individuals with Parkinson’s disease.

After sequencing the cell types, the researchers found that altered ANK1 expression originates in microglia, found in the brain and central nervous system, according to the study published in PLOS ONE.

The three of the cell types in this study came from the hippocampus, one of the first regions of the brain to suffer damage from Alzheimer’s, resulting in short-term memory loss and disorientation. Individuals with extensive damage to the hippocampus are unable to form and retain new memories.

Alzheimer’s features many signs of chronic inflammation, and microglia are key regulators of the inflammatory cascade, proposed as an early event in the development of Alzheimer’s, the study said.

Paper: “Source of cell-specific change in Alzheimer’s disease: ANK1 gene expression change found in brain’s microglia cells associated with neuroinflammation.”

Reprinted from materials provided by The Translational Genomics Research Institute.

 

Many aspects of Alzheimer’s disease remain a mystery, but scientists know that the disease’s progression involves the tau protein. In Alzheimer’s, the tau protein clumps together to form rope-like inclusions in brain cells that eventually strangle neurons. What has not been known until now is how the protein transitions from its liquid state to solid fibers.

Researchers have discovered a property of tau that helps explain how the protein can change from liquid to solid state. When tau is in a complex with RNA, it can condense into a compact “droplet”. During a process called phase separation, tau and RNA hold together without a membrane, but remain separate from the surrounding milieu, leading to highly concentrated tau that becomes vulnerable to aggregation.

The research demonstrated that up to eight tau molecules bind to the RNA, forming an extended fluidic assembly. Other proteins similar to tau also irreversibly aggregate in other neurodegenerative diseases, such as ALS, also known as Lou Gehrig’s disease.

Researchers plan to search for the counterpart of tau droplets in living cells. They will also study why and how cells regulate the formation of the droplets, and whether this could represent a possible path toward therapy.

Paper: “Neurodegenerative diseases: A biophysical smoking gun: Scientists begin to unravel how the protein tau transitions from a soluble liquid state to solid fibrous tangles”
Reprinted from materials provided by University of California – Santa Barbara.

New findings published in the journal Brain may help explain why poor sleep has been linked to the development of dementias such as Alzheimer’s. Previous studies have demonstrated that the risk of cognitive problems increases with poor sleep, but they were not able to explain why disrupted sleep caused damage to brains.

To better understand the link, researchers studied 17 healthy adults ages 35 to 65 who were given an activity monitor to measure their nightly sleep for at least five nights. The participants then spent a night at the School of Medicine in a specially designed sleep room. Half of them were randomly assigned to have their sleep interrupted by a series of beeps through headphones as soon as their brain signals settled into the slow-wave pattern that characterises deep sleep.  The beeps would continue until the participants’ brain patterns showed they had entered shallower sleep. The other half slept normally.

The next morning, those whose sleep was disrupted reported feeling tired and unrefreshed. The participants also underwent a spinal tap to measure the levels of amyloid beta and tau in their brain fluid and spinal cord. A month later, the participants came back again, but the uninterrupted sleep group had their sleep disrupted, while the interrupted sleep group was allowed to sleep normally.

Analysis of the participants’ amyloid beta and tau levels showed a 10 percent increase in amyloid beta levels after a single night of interrupted sleep, but no increase in tau levels. Increased tau levels were found in participants whose activity monitors recorded poor sleep for a week prior to the spinal tap.

While the study was not designed to determine whether better quality or more sleep can reduce the risk of Alzheimer’s, neither can hurt.

Paper: “Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels”
Reprinted from materials provided by Washington University in St. Louis.

A study published in Nature Communications announces a groundbreaking advancement which could potentially help patients requiring stem cell therapies for spinal cord injuries, stroke, Parkinson’s disease, Alzheimer’s disease, arthritic joints or any other condition requiring tissue regeneration.

Living organisms’ cells use a remarkable signaling machinery that has the capacity to switch signals on and off to activate complex processes. Until now, building artificial materials to replicate this dynamic capacity has been almost impossible.

The study reports the development of the first-ever synthetic material that has the capability to trigger reversibly this type of dynamic signaling. The platform could both lead to materials that manage stem cells for more effective regenerative therapies, and also allow scientists to study and develop new ways to control the fate of cells and their functions. One potential use of the new technology could help cure Parkinson’s disease. The patient’s own skin cells could be converted to stem cells using existing techniques. The new technology could help expand the newly converted stem cells in vitro, then signal them to differentiate into dopamine-producing neurons, which could then be transplanted back to the patient.

In the future, it may be possible to perform the process in vivo, using stem cells encapsulated in the new material injected directly into a targeted location. The patient would then receive soluble molecules to proliferate and differentiate the transplanted cells.

Paper: “New technology to manipulate cells could help treat Parkinson’s, arthritis, other diseases: DNA strands in materials act like traffic signals to start, stop cell activity or regenerate tissue”
Reprinted from materials provided by Northwestern University.

“P 28 Voxel-based Morphometry (VBM) subcortical white matter changes correlate with disease progression in amyotrophic lateral sclerosis” has been published in the journal Clinical Neurophysiology. This work was supported in part by JPND through the ONWebDUALS project, selected in the 2013 Preventive Strategies call, and through the SOPHIA project, selected in the 2011 Biomarkers call.

A team of researchers has identified two genes that influence a person’s risk of developing Alzheimer’s disease.

The new finding, which builds on previous work of identifying 24 susceptibility genes, enables a better understanding of the mechanisms underlying the disease and offers further hope in developing new treatments. The work was published in Nature Genetics.

The two novel genes, which were not previously considered candidates for Alzheimer’s risk, were identified during a study which compared the DNA of tens of thousands of individuals with Alzheimer’s with aged-matched people who are free from the disease.

In addition to these two genes, the researchers also discovered a possible network of other genes and proteins that may be implicated in the development of Alzheimer’s disease.  The study also suggested that immune cells could play a causal role in Alzheimer’s, which may lead to new treatment approaches and targets, the scientists report.

Finally, the researchers say that the genes identified in the study reinforce the importance of microglia, which are responsible for clearing up damaged cells and proteins.

Paper:“Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease”

Reprinted from materials provided by Cardiff University.

“P 30 Voxel-based intensometry of high resolution T1 MRI predicts disease progression in ALS” has been published in the journal Clinical Neurophysiology. This work was supported in part by JPND through the oNWebDUALS project, selected in the 2013 Preventive Strategies call, and through the SOPHIA project, selected in the 2011 Biomarkers call.

People at risk for Alzheimer’s disease who do more moderate-intensity physical activity, but not light-intensity physical activity, are more likely to have healthy patterns of glucose metabolism in their brain, according to a new study.

Results of the research were published in the Journal of Alzheimer’s Disease.

Researchers used accelerometers to measure the daily physical activity of participants, all of whom are in late middle-age and at high genetic risk for Alzheimer’s disease, but presently show no cognitive impairment. Activity levels were measured for one week, quantified, and analyzed. This approach allowed scientists to determine the amount of time each subject spent engaged in light, moderate, and vigorous levels of physical activity. Light physical activity is equivalent to walking slowly, while moderate is equivalent to a brisk walk and vigorous a strenuous run. Data on the intensities of physical activity were then statistically analyzed to determine how they corresponded with glucose metabolism — a measure of neuronal health and activity — in areas of the brain known to have depressed glucose metabolism in people with Alzheimer’s disease. To measure brain glucose metabolism, researchers used a specialized imaging technique called 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).

Moderate physical activity was associated with healthier (greater levels of) glucose metabolism in all brain regions analyzed. The researchers noted a step-wise benefit: subjects who spent at least 68 minutes per day engaged in moderate physical activity showed better glucose metabolism profiles than those who spent less time.

The researchers say that, in terms of next steps, they will focus on ongoing research striving to better elucidate the neuroprotective effect of exercise against Alzheimer’s disease.

Paper:“Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer’s Disease”
Reprinted from materials provided by IOS Press.