NeuroInflammation Critical in the Developement of Alzheimer’s

Doctors regard amyloid plaque lodged between the brain’s nerve cells and tangled tau protein fibers forming within the cells as the hallmark of Alzheimer’s disease. However, amyloid plaque — consisting of broken pieces of protein that clump together — is also present in the brains of older adults who do not develop Alzheimer’s, suggesting another factor is triggering the disease.

A new study finds that inflammation in the brain drives the progression from the presence of amyloid plaque and tau tangles to the onset of dementia and Alzheimer’s disease.
Lead author of the study, Dr. Tharick Pascoal, Ph.D., assistant professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, PA, explains:

Many [older adults] have amyloid plaques in their brains but never progress to developing Alzheimer’s disease. We know that amyloid accumulation on its own is not enough to cause dementia — our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment.”

While scientists have observed neuroinflammation in people with Alzheimer’s before, the new study reveals for the first time its critical role in the development of the disease. The research finds that activating the brain’s immune cells — its microglial cellspromotes the spread of tangled tau proteins that comprise amyloid plaque.

Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of medical and scientific relations, who was not involved in the study, explained the purpose of neuroinflammation to Medical News Today. The Alzheimer’s Association contributed funding to the research.

Inflammation has an important role in fighting off infection and other pathogens in the body, including in the brain and central nervous system,” said Snyder. Microglia “help clear debris (damaged neurons, infections) from the brain.” “However,” adds Dr. Snyder, “a sustained inflammatory response, or a change from acute to chronic neuroinflammation, may contribute to the underlying biology of several neurodegenerative disorders.

Inflammation is not by itself associated with cognitive impairment, daid Dr. Pascoal. “However when neuroinflammation converges with amyloid pathology, the interaction potentiates tau pathology. As a consequence, the coexistence of these three processes in the brain — amyloid, neuroinflammation, and tau pathology — determines cognitive deterioration.”

Results suggest that the combination of anti-amyloid with anti-inflammatory therapies in the early stages of the disease, when the pathology of tau is still confined to the temporal cortex, would maximize the efficacy of these drugs.”

The study appears in Nature Medicine.

Source: https://www.medicalnewstoday.com/

What is the Human Cortex?

The cerebral cortex is the thin surface layer of the brain found in vertebrate animals that has evolved most recently, showing the greatest variation in size among different mammals (it is especially large in humans). Each part of the cerebral cortex is six layered (e.g., L2), with different kinds of nerve cells (e.g., spiny stellate) in each layer. The cerebral cortex plays a crucial role in most higher level cognitive functions, such as thinking, memory, planning, perception, language, and attention. Although there has been some progress in understanding the macroscopic organization of this very complicated tissue, its organization at the level of individual nerve cells and their interconnecting synapses is largely unknown.

Petabyte connectomic reconstruction of a volume of human neocortex. Left: Small subvolume of the dataset. Right: A subgraph of 5000 neurons and excitatory (green) and inhibitory (red) connections in the dataset. The full graph (connectome) would be far too dense to visualize.

Mapping the structure of the brain at the resolution of individual synapses requires high-resolution microscopy techniques that can image biochemically stabilized (fixed) tissue. We collaborated with brain surgeons at Massachusetts General Hospital in Boston (MGH) who sometimes remove pieces of normal human cerebral cortex when performing a surgery to cure epilepsy in order to gain access to a site in the deeper brain where an epileptic seizure is being initiated. Patients anonymously donated this tissue, which is normally discarded, to our colleagues in the Lichtman lab. The Harvard researchers cut the tissue into ~5300 individual 30 nanometer sections using an automated tape collecting ultra-microtome, mounted those sections onto silicon wafers, and then imaged the brain tissue at 4 nm resolution in a customized 61-beam parallelized scanning electron microscope for rapid image acquisition.

Imaging the ~5300 physical sections produced 225 million individual 2D images. The team then computationally stitched and aligned this data to produce a single 3D volume. While the quality of the data was generally excellent, these alignment pipelines had to robustly handle a number of challenges, including imaging artifacts, missing sections, variation in microscope parameters, and physical stretching and compression of the tissue. Once aligned, a multiscale flood-filling network pipeline was applied (using thousands of Google Cloud TPUs) to produce a 3D segmentation of each individual cell in the tissue. Additional machine learning pipelines were applied to identify and characterize 130 million synapses, classify each 3D fragment into various “subcompartments” (e.g., axon, dendrite, or cell body), and identify other structures of interest such as myelin and cilia. Automated reconstruction results were imperfect, so manual efforts were used to “proofread” roughly one hundred cells in the data. Over time, the scientists expect to add additional cells to this verified set through additional manual efforts and further advances in automation.

Source: https://ai.googleblog.com/

Long-term memory forming mechanism discovered

Your brain has its own box of memories. If you were to hold it in your hand, brush off the dust and open it up, you’d be able to pull out Polaroid snaps of your most treasured memories. Your graduation ceremony perhaps, your wedding day, your daughter’s first words – all things you wouldn’t want to forget. But how does your brain keep these memories in their crystal-clear clarity? The strength of a memory lies in its formation and upkeep. When we create a memory, thin connections, called axons, form between nerve cells in our brain. The point at which two axons connect is called a synapse, and it is the strength of the synapse that determines if the memory is kept or allowed to fade away.

Now, a study in mice carried out by Nobel Prize-winning researchers at Columbia University has shown that a protein called CPEB3 plays an important role in the formation of memories. The team discovered how this protein is stored and used in the brain and hope it could lead to new methods of slowing memory loss in humans.

The science of how synapses form and are strengthened over time is important for deciphering any disorder in which synapses – and the memories associated with them – degrade and die, such as Alzheimer’s disease,” said Dr Luana Fioriti. CPEB3 is created by the brain’s memory centre, the Hyppocampus. Once produced, it is stored in chamber-like structures called P bodies that protect it from other parts of the cell. It then travels to the synapse between nerve cells where required and is gradually released to help create a specific memory.

The findings suggest that the more CPEB3 released at a synapse, the stronger the connection and thus, the more concrete the resulting memory is. When the protein was removed, the mice could create new memories but were unable to keep them.

Source: https://www.sciencefocus.com/

Growing New Cartilage To Eradicate Osteoarthritis Pain

What is graphene foam? It’s a synthetic “wonder material” made from the same carbon atoms that make up the lead in a pencilGraphene foam can be used as a “bioscaffold” to mesh with human stem cells and grow new cartilage. In addition to being incredibly strong, graphene foam conducts heat and electricity which helps neurons, or nerve cells, transmit information. Boise State researchers believe graphene foam-enhanced cartilage could one day be used to treat the joint pain caused by osteoarthritis as well as prevent the need for joint replacement. Osteoarthritis is incurable and affects half the U.S. population over the age of 65.

If we could take graphene foam, adhere a patient’s own stem cells on it then and inject that into someone’s knee to regrow their own cartilage, that would be the ‘pie in the sky,‘” said Dave Estrada, co-director of the Boise State University’s Advanced Nanomaterials and Manufacturing Laboratory.

A Boise State team led by Katie Yocham, a doctoral student in the Micron School of Materials Science and Engineering, and Estrada have published a study, “Mechanical Properties of Graphene Foam and Graphene Foam-Tissue Composites,” in the Advanced Engineering Materials journal.

While earlier studies at Boise State have shown that graphene foam is compatible with cells for growing new cartilage tissue, this is the first study to investigate how that tissue would actually function in a human joint under normal stresses, including high impact activities.

Trevor Lujan, an associate professor in the Department of Mechanical and Biomedical Engineering, and one of the authors of the study, praised Yocham’s work. “Katie’s strong efforts on this project have provided the biomedical community with a rigorous characterization of the bulk mechanical behavior of cellularized graphene foam. This baseline knowledge is an important step in the rising use of graphene foam for biomedical applications,” he said.

Estrada believes the biomedical use of graphene foam may have other applications, including in the military where a majority combat injuries involve the musculoskeletal system. “Our vision is to develop novel bioscaffolds that can expedite healing, reduce the need for amputation, and help save lives,” he added.

Source: https://news.boisestate.edu/

Graphene Strengthens Neuronal Activity

A work led by SISSA in Italy and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of iontrapping’ by graphene carpets and its effect on the communication between neurons.The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition.

Graphene is the thinnest bi-dimensional material available today, characterisedby incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.
A study conducted by SISSAScuola Internazionale Superiore di Studi
Avanzati, and the University of Trieste in association with the University of Antwerp (Belgium), the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now.

“It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped.
It is this small variation that determines the increase in neuronal
excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.
The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices“.

Source: https://www.sissa.it/