Shorter version Abeta (Abeta-38) protects against Alzheimer's

Shorter version Abeta (Abeta-38) protects against Alzheimer's


Findings from a new study on Alzheimer's disease (AD), could eventually help clinicians identify people at highest risk for developing the irreversible, progressive brain disorder and pave the way for treatments that slow or prevent its onset.

The research, published in the journal Scientific Reports has demonstrated that a shorter form of the protein peptide believed responsible for causing AD (beta-amyloid 42, or Aβ42) halts the damage-causing mechanism of its longer counterpart.

"While Aβ42 disrupts the mechanism that is used by brain cells to learn and form memories, Aβ38 completely inhibits this effect, essentially rescuing the brain cells," said the senior author.

Previous studies have hinted that Aβ38 might not be as bad as the longer form, said the author, but their research is the first to demonstrate it is actually protective.

"If we can specifically take out the Aβ42 and only keep the Aβ38, maybe that will help people live longer or cause the disease to start later, which is what we all want."

Aβ42 is toxic to cells, disrupts communication between cells, and over time accumulates to form deposits called plaques. This combination of factors is believed responsible for causing AD. Experts have long thought that all forms of Aβ peptides cause AD, despite the fact that clinical trials have shown removing these peptides from the brains of patients does not prevent or treat the disease.

The project confirmed the protective effects of the shorter protein across a variety of different analyses: in synthetic versions of the protein in test tubes; in human cells; in a worm model widely used for studying aging and neurodegeneration; in tissue preparations used to study membrane properties and memory; and in brain samples from autopsies. In the brain samples, they also found that men with AD who had more Aβ42 and less Aβ38 died at an earlier age. The fact that they didn't see this same pattern in samples from women suggests the protein peptide behaves differently in men and women..

While the author wasn't surprised to see that the shorter form prevents the damage caused by the longer version, he said he was a little taken aback at how significant an effect it had.

"As soon as you put Aβ38 into it, it brings it back up to control levels, completely inhibiting the toxic effects of Aβ42. That's what was pleasantly surprising."

https://news.usask.ca/articles/research/2021/usask-led-research-team-shows-alternate-form-of-brain-protein-that-causes-alzheimers-actually-protects-against-the-disease.php

https://www.nature.com/articles/s41598-020-80164-w

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fthe-a-946-1-38&filter=22

Edited

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