In a breakthrough, scientists have witnessed the point at which brain proteins turn into knots associated with Alzheimer’s disease.
In the study, published in the Journal of Biological Chemistry, researchers found giving less than a volt of electricity to tau proteins led to their entanglement.
For the uninitiated, tau proteins are found in abundance in the human brain. These proteins fold and bind together with structural elements called microtubules, and create a scaffold for brain cells to function properly.
However, tau proteins can sometimes fold inordinately. These abnormally folded tau proteins are a sign of Alzheimer’s in many, although not all, cases.
Called the neurofibrillary tangle, these knotted tau proteins are believed to interfere with cell function, ultimately leading to cell death.
Researchers at the University of California Santa Barbara (UCSB) posit that watching the tau proteins tangle in the lab provides a way to assess the protein’s role in brain degeneration. Furthermore, the technique can be used as a great model to test current and future treatments for neurodegenerative diseases.
In the study, researchers added less than a volt of electricity, and found it could trigger out-of-control tangling in a specific type of tau protein.
The current mimicked the molecular signals that naturally cause the “hyper-folding” of tau proteins. It allowed researchers to watch the tau proteins cross the “tipping point” as they transformed from healthy to diseased states.
“This method provides scientists a new means to trigger and simultaneously observe the dynamic changes in the protein as it transitions from good to bad,” biochemist Daniel Morse from UCSB, explained, ScienceAlert reported.
“Because we can turn on and fine-tune the process at will, we can use this system to see what molecules could interdict or block specific stages of folding and assembly,” Morse added.
Tau proteins are made up of a group of soluble variants, including the one called K18, which was used in the current study.
When K18 was stimulated by a volt of electricity over hours or days, the proteins tangled rapidly and irreversibly, the study found.
Interestingly, even with a brief exposure of just 15 minutes, tau proteins began to entangle, the study found. It is worth noting these tangles were easier to untangle with a reverse voltage.
The study suggests that tau tangling progresses over time, parallel to how symptoms of Alzheimer’s seem to do. The progression from a healthy to diseased tau protein, researchers wrote in the paper, could be “a gradual one rather than the result of a single all-or-none switch.”
Recently, a 19-year-old got diagnosed with Alzheimer’s disease at a memory clinic in China. Reportedly, the patient began experiencing memory decline at 17. His cognitive losses also got worse quickly, as imaging of his brain showed shrinkage in the hippocampus, the part involved in memory.