Development of plaques in Alzheimer's disease resolved

December 21, 2020

A team of researchers from Ruhr-Universität Bochum (RUB) and Vrije Universteit Amsterdam (VU) has determined the development stages of Aβ fibrils and has thus been able to understand the development of plaques. The researchers report in the academic journal Acta Neuropathologica Communications on 11 December 2020.

Joining forces

The team from the Centre for Protein Diagnostics (Prodi) at RUB is working with the Vrije Universiteit Medical Center (VUmc) in order to pool expertise in protein and dementia research. Medical experts such as Baayla Boon from VUmc attends to patients with dementia in the clinic and examines the post mortem brain tissue, which is diligently collected by the Netherlands Brain Bank (NBB). Razor-thin slices are cut from the brain for examination. "Such slices of tissue allow us to look deep within the convolutions of the brain," says Baaylas supervisor Professor Annemieke Rozemuller, Head of Neuropathology at VUmc.

The groups exchange samples and findings at regular meetings. In Bochum, protein researchers led by Professor Klaus Gerwert, Head of Biophysics and Founding Director of Prodi at RUB, examine the brain tissue. The plaques contained in this are illuminated with infrared light in special microscopes. "This allows us to determine the folding of biomarker proteins in the tissue," says Dominik Röhr from Prodi.

A new timeline for plaques

The formation of Aβ fibrils is well known from laboratory experiments. First, Aβ folds like a sheet of paper to form so-called β-sheets. These clump together into small groups, which are known as oligomers. Over time, the β-sheets come together like a deck of cards to form fibrils. The Bochum-based researchers led by Klaus Gerwert utilize this process as an internal clock for plaques. Newly developed plaques contain many oligomers. Over the course of plaque development, fibrils are continuously formed. The researchers thereby concluded that plaques pass through different stages during their development. "It has not been possible to directly observe the development of plaques so far. By combining methods from medicine and physics, new possibilities are now opening up," says Klaus Gerwert, delighted.

On the left is a fully developed plaque of brown-stained Aβ. On the right, the structure of Aβ determined by infrared microscopy is shown. In core are fibrils (red), around are mainly oligomers (blue).

Aβ is the focus in the fight against Alzheimer's disease. A central approach in the search for a cure is dissolving the plaques in the patients' brains. "Early diagnosis of Alzheimer's disease is crucial to prevent Aβ from causing irreparable damage in the brain," says Dominik Röhr. Promising medications are currently undergoing approval testing. These include the antibody aducanumab, which can break down plaques in the brain. The new findings from infrared microscopy indicate that the development of plaques could be stopped at an early stage by preventing the formation of oligomers. These are considered to be particularly harmful to the brain. The toxic effect of Aβ could thus be minimised with suitable drugs.
-end-


Ruhr-University Bochum

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.