New Discovery May Unlock the Secrets of Alzheimer’s Disease Through Stickier Than We Thought Protein Plaques

by Klaus Müller
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Studying the Connection between Amyloid Peptide, Alzheimer’s, and Other Diseases

Scientists from Rice University are doing experiments to learn more about a certain peptide linked to Alzheimer’s disease. The Centers for Disease Control and Prevention say that around 14 million people in the United States could have Alzheimer’s disease by the year 2060.

Angel Martí and his team have recently discovered something really cool. They used a technique called time-resolved spectroscopy along with some special chemistry to find an extra spot on the amyloid-beta aggregates (groups of molecules). This opens up new possibilities for cures for Alzheimer’s and other diseases connected to these types of molecules. The results were published in Chemical Science, which is a scientific journal.

In people with Alzheimer’s disease, deposits of something called amyloid plaque can be seen in the brain. This amyloid-beta is a thing that forms into tiny nano fibers and clumps together — like little piles of beads. Over time they grow bigger, and look like plaques. Professor Martí from Rice University describes them this way.

Learning how molecules attach to amyloid-beta is really important because it can help us make drugs that attach better and also learn who else is involved in damaging the brain.

The Martí group did some research and eventually discovered an area where amyloid-beta deposits could attach to. To figure this out, they used special molecules that glowed when checked under a spectroscope. This brightness was proof that they had found the right spot!

Time-resolved spectroscopy, which the lab used in its newest finding, is a research technique that looks at how long molecules take to become “excited”. To ‘excite’ these molecules, we use light so they can absorb the energy from it. Then, the molecule becomes more energetic and enters an “excited state”.

The molecules in amyloid-beta (a type of protein) give off a special glowing light. Scientists measure how long the molecules stay in an energized state to study how small molecules attach themselves to it. What’s more, they discovered that different colored dyes also bind to these deposits, surprising them!

Scientists are now able to make a map of places where proteins stick in amyloid-beta and also keep track of the amino acids needed for creating holes to trap proteins in the amyloid-beta fibres.

Time-resolved spectroscopy can tell us about the environment around dye molecules. Javier Martí used it to find that there was a second binding site. The fluorescence from free dye molecules in solution had one lifetime, but when the molecule was bound to amyloid fibers, the environment changed and two different lifetimes were observed.

We recently discovered something amazing. We were studying a molecule and found out that it was binding to two different sites, which is much more than the single site we expected from our earlier studies. That’s because the technologies we used before weren’t able to show us all of the parts of this molecule.

The scientists were excited by their discovery and decided to do some more experiments. They tested two different types of molecules to find out if one of them might be attracted to a protein called amyloid-beta. Surprisingly, even the molecule that wasn’t supposed to bind ended up being attracted to the amyloid-beta.

Martí said the new findings could help us learn more about illnesses connected to amyloid proteins, like Parkinson’s, ALS, Type 2 diabetes and systemic amyloidosis. We can also use it to find out about good uses for amyloids like medicines and materials.

According to Martí, our bodies and other organisms can make different kinds of amyloids for multiple reasons, such as creating protective barriers or storing chemicals. Some even produce ones that fight against bacteria. This field of science is increasing in popularity, so our findings could open up possibilities for further research.

This passage is about a research paper published in the journal Chemical Science on January 19, 2023. The paper talks about how to learn more about something called amyloid nanofibrils by using time-resolved spectroscopy. It was written by Bo Jiang and 8 other scientists, who wanted to figure out what special parts make up these amyloid nanofibrils. This could help us in the future understand better many things related to it!

Reference: “High Soluble Amyloid-ß42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations” by Andrea Sturchio, Alok K. Dwivedi, Tarja Malm, Matthew J.A. Wood, Roberto Cilia, Jennifer S. Sharma, Emily J. Hill, Lon S. Schneider,Neill R. Graff-Radford, Hiroshi Mori, Georg Nübling, Samir El Andaloussi, Per Svenningsson, Kariem Ezzat, Alberto J. Espay and the Dominantly Inherited Alzheimer Consortia (DIAN), 16 September 2022, Journal of Alzheimer’s Disease.
DOI: 10.3233/JAD-220808

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