Researchers from the University of Saskatchewan have revealed a potential biomarker for Alzheimer’s disease. Their findings may help identify those at higher risk of developing the brain disorder and serve as the basis for future treatments.

The study, which was led by Darrell Mousseau, a professor in the department of psychiatry, examined a variant in the presenilin-1 (PSEN1) gene. 

Mousseau performed the study alongside U of S professors Chris Eskiw and Michael Wu with the purpose of investigating how the PSEN1 variant relates to premature aging.

The PSEN1 gene encodes for presenilin-1, an integral component of the enzyme responsible for breaking down the amyloid precursor protein — a protein linked to brain development and function. Presenilin-1 helps to break down the bonds between amino acids, resulting in beta-amyloid (Aβ) peptides.

Mousseau explained that, under normal circumstances, the amyloid precursor protein is broken down to generate a peptide that is 40 amino acids in length, better known as beta-amyloid 40 (Aβ40). In individuals with Alzheimer’s, however, that same peptide is composed of 42 amino acids, better known as beta-amyloid 42 (Aβ42). 

“Those extra two amino acids are incredibly hydrophobic, and they make that otherwise useful peptide become neurotoxic,” Mousseau said. The hydrophobicity of the added amino acids alters the structure of the peptide so that it does not perform its normal function.

Mousseau explained that the accumulation of Aβ42 disrupts how brain cells learn and form memories, resulting in complications most commonly associated with Alzheimer’s.

“In the Alzheimer’s brain, these cells start to lose their structure and with that happening, the ability to connect and communicate with other cells farther away in another brain region is lost, and most likely, irretrievably lost.”

Mousseau explained that the PSEN1 gene variant could be used as a biomarker for the early detection of Alzheimer’s and other age-related diseases, opening the door for therapies that may alter disease progression and treat symptoms before they appear.

“If we can target people 20 years before symptoms really emerge, we might get that individual an extra five or six years of normal life,” Mousseau said.

In a separate study, Mousseau and other researchers from the U of S demonstrated that a shorter form of the protein peptide, beta-amyloid 38 (Aβ38), may prolong the development of Alzheimer’s.

“The question was, if two more amino acids is worse, what about two less?” Mousseau asked.

The research team included medical student Maa Quartey, Jennifer Nyarko from the Cell Signalling Laboratory and department of psychiatry, U of S professors Carlos Carvalho and Scot Leary, and Jason Maley, lab manager of the Saskatchewan Structural Sciences Centre.

While previous studies have shown that Aβ38 is not as harmful as Aβ42, the study led by Mousseau is the first to show that it is actually protective against Alzheimer’s.

The study found that men diagnosed with Alzheimer’s who had more Aβ42 and less Aβ38 died at an earlier age, further demonstrating the inhibitory effects of the shorter peptide. 

Mousseau says that the study disproves a lot of what we know about Alzheimer’s and other age-related diseases.

“One of the things that we invariably find with every one of our projects is that it does not align very well with what’s already published,” Mousseau told the Sheaf. “We find ourselves at odds with a lot of our peers, but that’s what science is all about — we don’t just publish to confirm, we publish what we find.”

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Jakob Philipchuk | Staff Writer

Photo: Supplied by Darrell Mousseau