Inflammation, Key For The Progression of Alzheimer’s

According to a study by scientists of the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn now published in the journal “Nature”, inflammatory mechanisms caused by the brain’s immune system drive the progression of Alzheimer’s disease. These findings, which rely on a series of laboratory experiments, provide new insights into pathogenetic mechanisms that are believed to hold potential for tackling Alzheimer’s before symptoms manifest. The researchers envision that one day this may lead to new ways of treatment. Further institutions both from Europe and the US also contributed to the current results.

Alzheimer’s disease is a devastating neurodegenerative condition ultimately leading to dementia. An effective treatment does not yet exist. The disease is associated with the aberrant aggregation of small proteins called “Amyloid-beta” () that accumulate in the brain and appear to harm neurons. In recent years, studies revealed that deposits of , known as “plaques”, trigger inflammatory mechanisms by the brain’s innate immune system. However, the precise processes that lead to neurodegeneration and progression of pathology have thus far not been fully understood.

Deposition and spreading of Aβ pathology likely precede the appearance of clinical symptoms such as memory problems by decades. Therefore, a better understanding of these processes might be a key for novel therapeutic approaches. Such treatments would target Alzheimer’s at an early stage, before cognitive deficits manifest,” says Prof. Michael Heneka, a senior researcher at the DZNE and Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University of Bonn.

Prof. Heneka, who is also involved in the cluster of excellence “ImmunoSensation” at the University of Bonn, and coworkers have been investigating the role of the brain’s immune response in the progression of Aβ pathology for some time already. Previous work by the group that was published in Nature in 2013, had established that the molecular complex NLRP3, which is an innate immune sensor, is activated in brains of Alzheimer’s patients and contributes to the pathogenesis of Alzheimer’s in the murine model. NLRP3 is a so-called inflammasome that triggers production of highly pro-inflammatory cytokines. Furthermore, upon activation, NLRP3 forms large signaling complexes with the adapter protein ASC, which are called “ASC specks” that can be released from cells. “The release of ASC specks from activated cells has so far only been documented in macrophages and their relevance in disease processes has so far remained a mystery,” says Prof. Eicke Latz, director of the Institute of Innate Immunity and member of the cluster of excellence “ImmunoSensation” at the University of Bonn.


Car Pollution: Nanoparticles Travel Directly From The Nose To The Brain

The closer a person lives to a source of pollution, like a traffic dense highway, the more likely they are to develop Alzheimer’s or dementia, according to a study by the University of Southern California (USC) that has linked a close connection to pollution and the diseases. In a mobile lab, located just off of one of Los Angeles’ busiest freeways, USC scientists used a state-of-the-art pollution particle collector capable of gathering nano-sized particulate matter.

car pollution


We have shown that, as you would expect, the closer you get to the sources of these particles in our case the freeways, the higher the concentrations. So there is an exponential decay with distance. That means basically that, the concentration of where we are right now and if we were, let’s just say 20 or 10 or 50 yards from the freeway, those levels would be probably 10 times higher than where we are right now,” says Costas Sioutas, USC Professor of Environmental Engineering.

That means proximity to high concentrations of fossil fuel pollution, like a congested freeway, could be hazardous. Particulate matter roughly 30 times thinner than the width of a human hair, called PM2.5, is inhaled and can travel directly through the nose into the brain. Once there, the particles cause inflammatory responses and can result in the buildup of a type of plaque, which is thought to further the progression of Alzheimer’s. “Our study brought in this new evidence and I would say probably so far the most convincing evidence that the particle may increase the risk of dementia. This is really a public health problem. And I think the policy makers need to be aware of that, the public health risk associated with high level of PM2.5,” explains Jiu-Chiuan Chen, Associate Professor of Preventive Medicine.

USC researchers analyzed the data of more than 3,500 women who had the APOE4 gene, the major known risk-factor gene for Alzheimer’s disease. It showed that, over the course of a decade, the women who lived in a location with high levels of the PM2.5 pollution were 92 percent more likely to develop dementia.


How To Prevent Alzheimer’s

Researchers from Imperial College London (ICL) have prevented the development of Alzheimer’s disease in mice by using a virus to deliver a specific gene into the brain. The early-stage findings by scientists open avenues for potential new treatments for the disease. In the study, published in the journal Proceedings of the National Academy of Sciences, the team used a type of modified virus to deliver a gene to brain cells.

Previous studies by the same team suggest this gene, called PGC1 – alpha, may prevent the formation of a protein called amyloid-beta peptide in cells in the lab. Amyloid-beta peptide is the main component of amyloid plaques, the sticky clumps of protein found in the brains of people with Alzheimer’s disease. These plaques are thought to trigger the death of brain cellsAlzheimer’s disease affects around 520,000 people in the UK. Symptoms include memory loss, confusion, and change in mood or personality. Worldwide 47.5 million people are affected by dementia – of which Alzheimer’s is the most common form. There is no cure, although current drugs can help treat the symptoms of the disease.

Dr Magdalena Sastre, senior author of the research from the Department of Medicine at Imperial, hopes the new findings may one day provide a method of preventing the disease, or halting it in the early stages.


She explained: “Although these findings are very early they suggest this gene therapy may have potential therapeutic use for patients. There are many hurdles to overcome, and at the moment the only way to deliver the gene is via an injection directly into the brain. However this proof of concept study shows this approach warrants further investigation.”

The modified virus used in the experiments was called a lentivirus vector, and is commonly used in gene therapy explained Professor Nicholas Mazarakis, co-author of the study from the Department of Medicine: “Scientists harness the way lentivirus infects cells to produce a modified version of the virus, that delivers genes into specific cells. It is being used in experiments to treat a range of conditions from arthritis to cancer. We have previously successfully used the lentivirus vector in clinical trials to deliver genes into the brains of Parkinson’s disease patients.


Foot: Real-time Measurements Of Each Hit That A Player Endures

American football is a collision sport. And one consequence of repeated collisions between players is concussions. Science is starting to draw a link between these so-called mild brain injuries and the long-term effects they have on the players—namely the onset of chronic traumatic encephalopathy (CTE), a degenerative condition believed to be caused by head trauma and linked to depression and dementia. Recently, the issue has come to a head with the deaths of several former star players and the broadcast of the Frontline report “League of Denial,” which chronicles scientists’ long struggle to convince NFL officials to recognize a link between concussions and CTE.

While the NFL has tried to institute rules aimed at limiting the number of concussions that players suffer, the new regulations don’t seem to have stemmed the tide of brain injuries. Each week, a slew of player concussions are reported.

Another avenue being pursued in the hopes of limiting player concussions is the engineering of better helmets to improve head protection. An IEEE Spectrum article published last year, “Ratings for Football Helmets Help Improve Player Safety—But Not Before Another Tragedy,” reported on efforts to measure the effectiveness of different football helmets in reducing head trauma and categorize them based on their efficacy. Now researchers at Brigham Young University have taken this measurement of helmet impact one step further with immediate, real-time measurements of each hit that a player endures. From those measurements, which are communicated immediately to a hand-held device, coaches know whether a collision is capable of inducing a concussion, even if the player denies any problem.

A coach will know within seconds exactly how hard their player just got hit,” said Jake Merrell, a student at BYU who developed the technology, in a press release. “Even if a player pops up and acts fine, the folks on the sidelines will have data showing that maybe he isn’t OK.”

The heart of the technology is smart foam enabled by nanoparticles, which Merrell has dubbed “ExoNanoFoam.” The nano-enabled foam behaves as a piezoelectric in which pressure on the material produces an electrical voltage. A microcontroller sensor in the helmet reads the electrical voltage produced by the foam, and sends a signal to a handheld tablet equipped with a program that interprets it and delivers real-time information on the seriousness of the hit sustained by the player.

Since the foam is actually in contact with the player’s head, it provides a more accurate measurement of the forces upon the player’s head than the accelerometers that have been used previously to measure these impacts. The drawback with accelerometers is that they measure only of the acceleration or deceleration of the player’s helmet.