Findings from a new study of Alzheimer’s disease (AD), led by researchers at the University of Saskatchewan (USask), could ultimately help clinicians identify people at greatest risk for developing incontinent, progressive brain disorders and paving the way for slow or discontinued treatments.
The research, published in the journal Scientific Reports in early January, a shorter formulation of the protein peptide believed to be responsible for AD (beta-amyloid 42, or Aβ42) has been shown to block a mechanism that causes damage against no longer.
While Aβ42 disrupts the apparatus that brain cells use to learn and create memories, Aβ38 completely counteracts this effect, essentially rescuing the brain cells. “
Darrell Mousseau, Molecular Neurochemist, Professor, Department of Psychology and Head of USask, Cell Marking Laboratory
Previous studies have hindered that Aβ38 may not be as bad as the longer form, Mousseau said, but their research is the first to prove it is immune.
“If we can specifically take out the Aβ42 and keep the Aβ38 alone, that may help people live longer or cause the disease to start later, which is what we are. all want. “
Aβ42 is toxic to cells, disrupts communication between cells, and over time it accumulates to form deposits called plaques. This combination of factors is believed to be responsible for causing AD. Experts have long believed that all types of Aβ peptides cause AD, despite the fact that clinical trials have shown that removal of these peptides from patients’ brains does not inhibit or prevent treatment of the disease.
Mousseau said the idea behind the study was simple enough: If two other amino acids are bad, what about two less?
“We were just thinking: Let’s compare these three peptides, the 40 amino acids that most people have, the 42 amino acids that we think are involved in Alzheimer’s , and this 38, the slightly shorter version, “said Mousseau, who is Saskatchewan ‘s Chair of Research in Alzheimer’ s disease and related dementias, a position co – funded by the Saskatchewan Health Research Foundation and the Saskatchewan Alzheimer ‘s Society.
The project confirmed the protective effects of the shortest protein over several analyzes: in synthetic versions of the protein in test tubes; in human cells; in a worm model widely used for the study of age and neurodegeneration; in print preparation used to study organ and memory features; 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. Given that they did not observe this same pattern in samples from females, the protein peptide appears to behave in both males and females.
The USask team also included Maa Quartey and Jennifer Nyarko from the Cell Signal Lab (Department of Psychology), Jason Maley at the Saskatchewan Center for Structural Sciences, Carlos Carvalho in the Department of Biology, and Scot Leary in the Department of Biochemistry , Microbiology and Immunology. Joseph Buttigieg at Regina University and Matt Parsons at Memorial University of Newfoundland were also part of the research team.
While Mousseau was not surprised to see that the shorter form prevents the damage done by the longer version, he said he was a little taken aback by the size of the short version. effect.
“As soon as you inject Aβ38, it brings it back to control levels, completely counteracting the toxic effects of Aβ42. That was a pleasant surprise.”
Source:
University of Saskatchewan
Magazine Reference:
Fourth, MO, et al. (2021) The peptide Aβ (1–38) is a negative regulator of the peptide Aβ (1–42) involved in the progression of Alzheimer’s disease. Scientific Reports. doi.org/10.1038/s41598-020-80164-w.