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Our simulations show that amyloid beta, the substance underlying plaque aggregates that eventually is killing brain cells in Alzheimer's disease, should be able to diffuse out to the blood vessels. This is in contrast to a recent popular theory that the brain  fluid flows like rivers through the tiny clefts around the brain cells, bringing the waste products along. It is, however, not possible to measure the pressure differences within these tiny clefts. We solved this by using electron microscopy images of the clefts and then simulating the flow through these clefts. This required huge simulations, solving 100 million differential equations, and to our surprise we found that brain fluid will not be able to flow like rivers thorough the extracellular volumes. The cleft are too narrow. However, simulations revealed that amyloid and other waste products is transported out of these clefts by diffusion, the same mechanism  bringing molecules of smell into your nose in a room....

By combining different brain research methods in a versatile manner the researchers showed for the first time that transcranial magnetic stimulation of the brain targeting the prefrontal cortex can improve a test subject's ability to evaluate his or her performance in a tactile working memory task. The ability of human subjects to monitor and control their own cognitive processes is called metacognition. Metacognition is important for people and in many neuropsychiatric illnesses, it is possible to recognize that it has weakened. 'The patient's reduced sense of being ill is familiar from conditions such as Alzheimer's disease, schizophrenia, and traumatic brain injury. Understanding the brain function of healthy test subjects could help in the development of new treatment methods for neuropsychiatric illnesses in the future,' says Doctoral Candidate Juha Gogulski. Safe method Transcranial magnetic stimulation refers to a method in which the nerve cells o...

Gierasch says, "This one presented us with quite a scientific challenge, because all the techniques we usually use to look at communication between the different domains in proteins get stuck when the targets are flexible and not rigid, and the interdomain linker in Hsp70s is very flexible. We had to be clever in our approach." Details are in the  Journal of Biological Chemistry . As she explains, heat shock proteins in the Hsp70 family - molecular weight 70 - are "a really important class of molecular chaperones that have many important jobs in the cell, including binding to client proteins to assist their folding, or to keep them from pathologically aggregating, or to keep them unfolded so they can pass threadlike through a membrane." She describes the three parts of a folded Hsp70 protein as a nucleotide -binding domain and substrate-binding domain linked by a "mysterious" interdomain linker, which becomes part of the structure when a small molec...

Led by Todd Cohen, PhD, assistant professor of neurology, UNC scientists used human cell cultures to show how amyloid beta can trigger a dramatic inflammatory response in immune cells and how that interaction damages neurons. Then they showed how that kind of neuron damage leads to the formation of bead-like structures filled with abnormal tau protein . Similar bead-like structures are known to form in the brain cells of people with Alzheimer's disease. The UNC researchers also identified two proteins -- MMP-9 and HDAC6 -- that help promote this harmful, amyloid-to-inflammation-to-tau cascade. These proteins and others associated with them could become drug targets to treat or prevent Alzheimer's. "It's exciting that we were able to observe tau -- the major Alzheimer's protein -- inside these beaded structures," said Cohen, who is also a member of the UNC Neuroscience Center. "We think that preventing these structures from forming would leave people...

Independently from each other, two research groups have now revealed the molecular mechanism behind this mutation. Their research, published in  EMBO Molecular Medicine , sheds light on the role of TREM2 in normal brain function and suggests a new therapeutic target in Alzheimer's disease treatment. Alzheimer's disease, just like other neurodegenerative diseases, is characterized by the accumulation of specific protein aggregates in the brain. Specialized brain immune cells called microglia strive to counter this process by engulfing the toxic buildup. But as the brain ages, microglia eventually lose out and fail to rid all the damaging material. TREM2 is active on microglia and enables them to carry out their protective function. The protein spans the microglia cell membrane and uses its external region to detect dying cells or lipids associated with toxic protein aggregates. Subsequently, TREM2 is cut in two. The external part is shed from the protein and released, whil...

A ‘patched’ neuron: Inexperienced reveals the fluorescent protein used to information the robotic. Crimson reveals the fluorescent dye contained in the pipette. Yellow reveals the patched cell. Credit score: Picture courtesy of Imperial Faculty London Complete-cell patch clamp electrophysiology , or whole-cell recording (WCR), is the gold-standard approach for learning the behaviour of mind cells referred to as neurons below completely different mind states comparable to stress or studying. The process has been utilized in mammals because it was developed within the 1970s. It helps scientists to know mind perform and mind issues comparable to Alzheimer's. They do that by wanting on the electrical exercise of particular person neurons in a stay mammal mind to construct an even bigger image of its perform as a complete organ. This info is used to know the position perform in human mind issues. Nonetheless, WCR is notoriously difficult to carry out due to the smal...