New Brain Death Pathway In Alzheimer’s Identified

Findings of team led by the Arizona State University (ASU) scientists offer hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression
Alzheimer’s disease tragically ravages the brains, memories and, ultimately, personalities of its victims. Now affecting 5 million Americans, Alzheimer’s disease is the sixth-leading cause of death in the U.S., and a cure for Alzheimer’s remains elusive, as the exact biological events that trigger it are still unknown.

In a new study, Arizona State University-Banner Health neuroscientist Salvatore Oddo and his colleagues from Phoenix’s Translational Genomics Research Institute (TGen) — as well as the University of California, Irvine, and Mount Sinai in New York — have identified a new way for brain cells to become fated to die during Alzheimer’s disease. The research team has found the first evidence that the activation of a biological pathway called necroptosis, which causes neuronal loss, is closely linked with Alzheimer’s severity, cognitive decline and extreme loss of tissue and brain weight that are all advanced hallmarks of the disease.

We anticipate that our findings will spur a new area of Alzheimer’s disease research focused on further detailing the role of necroptosis and developing new therapeutic strategies aimed at blocking it,” said Oddo, the lead author of this study, and scientist at the ASU-Banner Neurodegenerative Disease Research Center at the Biodesign Institute and associate professor in the School of Life Sciences.

Necroptosis, which causes cells to burst from the inside out and die, is triggered by a triad of proteins. It has been shown to play a central role in multiple sclerosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), and now for the first time, also in Alzheimer’s disease.

There is no doubt that the brains of people with Alzheimer’s disease have fewer neurons,” explained Oddo. “The brain is much smaller and weighs less; it shrinks because neurons are dying. That has been known for 100 years, but until now, the mechanism wasn’t understood.
The findings appear in the advanced online edition of Nature Neuroscience.

Source: https://asunow.asu.edu/

Damaged teeth can be regrown naturally

A way to naturally regrow damaged teeth has been discovered by scientists in a breakthrough that could significantly reduce the need for fillings. Researchers at King’s College London (KCL) found that a drug designed to treat Alzheimer’s disease was able to stimulate the tooth to create new dentine capable of filling in large cavitiesTeeth can already cope with small areas of damage using the same process, but when the holes become too large a dentist must insert artificial cements or the tooth will be lost.

dentistCLICK ON THE IMAGE TO ENJOY THE VIDEO

The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine,” said Professor Paul Sharpe, lead author of a paper in the journal Scientific Reports.  “In addition, using a drug that has already been tested in clinical trials for Alzheimer’s disease provides a real opportunity to get this dental treatment quickly into clinics.”

If a tooth is damaged or infected, the soft inner pulp can become exposed, risking further infection. When this happens, a band of dentine, the hard material that makes up most of the tooth, will attempt to bridge the gap and seal off the pulp. But the researchers found that the natural repair mechanism could be boosted if the drug  Tideglusib was used. Previously it has been trialled as a treatment for various neurological disorders, including Alzheimer’s. It works by stimulating stem cells, which can turn into any type of tissue in the body, already present in the pulp to create new dentine.

The drug and a substance called glycogen synthase kinase were applied to the tooth on a biodegradable sponge made from collagen. As the sponge degraded, it was replaced by dentineleading to complete, natural repair”, according to a statement about the research issued by KCL.

Source: http://www.independent.co.uk/

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.

alzheimer_s_disease_vs_normal-spl

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.

Source: http://www3.imperial.ac.uk/

Implanted Neural Nanocomputers To Boost Failing Human Brains

As neural implants become more and more advanced, researchers think humans may be able to overcome diseases and defects like strokes and dementia with the help of nanocomputers in our brains.

With the forecasted inevitable rise of the machines — be they robots or artificial intelligences — humans are beginning to realize that they should work to maintain superiority. There are a few ideas about how we should do it, but perhaps the most promising option is to go full cyborg. (What could possibly go wrong?) On Monday, a company called Kernel, announced that it would be leading the charge.

Active_brain

The idea is something straight out of dorm room pot-smoking sessions. What if, the exhaling sophomore muses, we put computers inside our brains? Unfortunately for prospective stoner-scientists, the actual creation of such a device — a functioning, cognitive-enhancing neural implant — has long evaded bioengineers and neuroscientists alike.

Kernel thinks it’s past time to make real progress. Theodore Berger runs the Univerity of Southern California’s Center for Neural Engineering, and he caught the eye of Bryan Johnson, a self-made multimillionaire who’s obsessed with augmenting human intelligence. With Johnson’s entrepreneurial money and Berger’s scientific brain, the two launched Kernel.
For now, Berger and Johnson are focusing on achievable goals with immediate impacts. They are creating an analogous human neural implant that can mitigate cognitive decline in those who suffer from Alzheimer’s and the aftereffects of strokes, concussions, and other brain injuries or neurological diseases. If Kernel is able to replicate even the 10 percent cognitive improvement that Berger demonstrated in monkeys, those who suffer from these cognitive disorders will be that much more capable of forming memories and living out enjoyable lives.

Source: https://www.inverse.com/

Cheap Biosensor Detects Alzheimer’s, Cancer, Parkinson’s

A biosensor developed by researchers at the National Nanotechnology Laboratory (LNNano) in Campinas, São Paulo State, Brazil, has been proven capable of detecting molecules associated with neurodegenerative diseases and some types of cancer.

biosensor LNNano

The device is basically a single-layer organic nanometer-scale transistor on a glass slide. It contains the reduced form of the peptide glutathione (GSH), which reacts in a specific way when it comes into contact with the enzyme glutathione S-transferase (GST), linked to Parkinson’s, Alzheimer’s and breast cancer, among other diseases. The GSH-GST reaction is detected by the transistor, which can be used for diagnostic purposes.

The project focuses on the development of point-of-care devices by researchers in a range of knowledge areas, using functional materials to produce simple sensors and microfluidic systems for rapid diagnosis.

Platforms like this one can be deployed to diagnose complex diseases quickly, safely and relatively cheaply, using nanometer-scale systems to identify molecules of interest in the material analyzed,” explained Carlos Cesar Bof Bufon, Head of LNNano’s Functional Devices & Systems Lab (DSF) and a member of the research team for the project, whose principal investigator is Lauro Kubota, a professor at the University of Campinas’s Chemistry Institute (IQ-UNICAMP).

In addition to portability and low cost, the advantages of the nanometric biosensor include its sensitivity in detecting molecules, according to Bufon.

This is the first time organic transistor technology has been used in detecting the pair GSH-GST, which is important in diagnosing degenerative diseases, for example,” he explained. “The device can detect such molecules even when they’re present at very low levels in the examined material, thanks to its nanometric sensitivity.” A nanometer (nm) is one billionth of a meter (10-9 meter), or one millionth of a millimeter.

The system can be adapted to detect other substances, such as molecules linked to different diseases and elements present in contaminated material, among other applications. This requires replacing the molecules in the sensor with others that react with the chemicals targeted by the test, which are known as analytes.

Source: http://www.eurekalert.org/

How To Detect Alzheimer’s Disease Early

No methods currently exist for the early detection of Alzheimer’s disease, which affects one out of nine people over the age of 65. Now, an interdisciplinary team of Northwestern University scientists and engineers has developed a noninvasive MRI (magnetic resonance imaging) approach that can detect the disease in a living animal. And it can do so at the earliest stages of the disease, well before typical Alzheimer’s symptoms appear.

Led by neuroscientist William L. Klein and materials scientist Vinayak P. Dravid, the research team developed an MRI probe that pairs a magnetic nanostructure (MNS) with an antibody that seeks out the amyloid beta brain toxins responsible for onset of the disease. The accumulated toxins, because of the associated magnetic nanostructures, show up as dark areas in MRI scans of the brain. This ability to detect the molecular toxins may one day enable scientists to both spot trouble early and better design drugs or therapies to combat and monitor the disease. And, while not the focus of the study, early evidence suggests the MRI probe improves memory, too, by binding to the toxins to render them “handcuffed” to do further damage.
neurons
Fluorescent amyloid beta oligomers (green), bound to cultured hippocampal neurons, were detected with greater than 90 percent accuracy by the magnetic nanostructure probe (red)
We have a new brain imaging method that can detect the toxin that leads to Alzheimer’s disease,” said Klein, who first identified the amyloid beta oligomer in 1998. He is a professor of neurobiology in the Weinberg College of Arts and Sciences. “Using MRI, we can see the toxins attached to neurons in the brain,” Klein said. “We expect to use this tool to detect this disease early and to help identify drugs that can effectively eliminate the toxin and improve health.
Source: http://www.northwestern.edu/

Transplant New Brain Cells And Forget Alzheimer’s

A new study from the Gladstone Institutes has revealed a way to alleviate the learning and memory deficits caused by apoE4, the most important genetic risk factor for Alzheimer’s disease, improving cognition to normal levels in aged mice.

In the study, which was conducted in collaboration with researchers at UC San Francisco and published in the Journal of Neuroscience, scientists transplanted inhibitory neuron progenitors—early-stage brain cells that have the capacity to develop into mature inhibitory neurons—into two mouse models of Alzheimer’s disease, apoE4 or apoE4 with accumulation of amyloid beta, another major contributor to Alzheimer’s. The transplants helped to replenish the brain by replacing cells lost due to apoE4, regulating brain activity and improving learning and memory abilities.

Brain Cells

This is the first time transplantation of inhibitory neuron progenitors has been used in aged Alzheimer’s disease models,” said first author Leslie Tong, a graduate student at the Gladstone Institutes and UCSF. “Working with older animals can be challenging from a technical standpoint, and it was amazing to see that the cells not only survived but affected activity and behavior.

The success of the treatment in older mice, which corresponded to late adulthood in humans, is particularly important, as this would be the age that would be targeted were this method ever to be used therapeutically in people.

Source: http://gladstoneinstitutes.org/

Alzheimer’s: Amazing News From The Nano World

Alzheimer substance, amyloid, may be the nanomaterial of tomorrow. Amyloid protein causes diseases like Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob . Researchers from Chalmers University of Technology recently unveiled an unexpected discovery about amyloid in an article published in the Nature Photonics journal. Amyloids are misfolded variants of proteins that occur naturally in the body. The researchers have now shown that the misfolded variants react to multiphoton irradiation, a type of laser effect, whereas the healthy proteins do not.

The discovery could be useful in a variety of fields. Not only can it lead to new methods to detect and treat the brain diseases that amyloid causes, amyloid may also be used as a building block for future nanomaterials.
Amyloid proteinAmyloid protein causes diseases like Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease. But amyloid also carries unique characteristics that may lead to the development of new composite materials for the nano processors and data storage of tomorrow, and even make objects invisible
It is possible to create these protein aggregates artificially in a laboratory”, says Piotr Hanczyc, one of the researchers who made the discovery. “By combining them with other molecules, one could create materials with unique characteristics.
The amyloid aggregates are as hard and rigid as steel. The difference is that steel is much heavier and has defined material properties, whereas amyloids can be tuned for specific purposes. By attaching a material’s molecules to the dense amyloid, its characteristics change.
“This was already known, but what has not been known is that the amyloids react to multiphoton irradiation”
”, says Piotr Hanczyc. “This opens up new possibilities to also change the nature of the material attached to the amyloids“.
Source: http://www.mynewsdesk.com/

APOE4 Gene Increases Up To Ten-Fold Risk To Develop Alzheimer’s

A research team from Columbia University Medical Center (CUMC) identified key molecular pathways that link genetic risk factors to Alzheimer’s disease. More specifically, the researchers first focused on the single most significant genetic factor that puts people at high risk for Alzheimer’s, called APOE4 (found in about a third of all individuals). People with one copy of this genetic variant have a three-fold increased risk of developing late-onset Alzheimer’s, while those with two copies have a ten-fold increased risk. “In this study,” said Dr. Abeliovich, “we initially asked: If we look at autopsy brain tissue from individuals at high risk for Alzheimer’s, is there a consistent pattern?” Surprisingly, even in the absence of Alzheimer’s disease, brain tissue from individuals at high risk (who carried APOE4 in their genes) harbored certain changes reminiscent of those seen in full-blown Alzheimer’s disease,” said Dr. Abeliovich. “We therefore focused on trying to understand these changes, which seem to put people at risk. The brain changes we considered were based on ‘transcriptomics’—a broad molecular survey of the expression levels of the thousands of genes expressed in brain.”
Human-neuronsThe researchers evaluated the role of SV2A, using human-induced neurons that carry the APOE4 genetic variant. (The neurons were generated by directed conversion of skin fibroblasts from individuals at high risk for Alzheimer’s, using a technology developed in the Abeliovich laboratory.) Treating neurons that harbor the APOE4 at-risk genetic variant with levetiracetam (which inhibits SV2A) led to reduced production of amyloid beta. The study also showed that RFN219 appears to play a role in APP-processing in cells with the APOE4 variant.
Source: http://newsroom.cumc.columbia.edu/