Alzheimer's disease remains incurable but great advances have been made in understanding the disease. The latest discovery is that a gene, which hadn't been considered a factor in Alzheimer's, is very much so: it affects patient vulnerability to the toxic effects of amyloid- plaques.
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Specifically, reduced expression of RGS2 heightens the susceptibility of brain nerve cells to the damaging effects of the plaque associated with Alzheimer's.
Amyloid- is a protein that is chemically sticky by nature, so it has a tendency to clump. Even small clumps can block signals between nerve cells. Big clumps become actual plaque in our brains, which is one of the hallmarks of Alzheimer's.
Theoretically, boosting the expression of the gene RGS2 (which stands for "Regulator of Protein Signaling 2") could reduce sensitivity to the plaque, slowing or halting the progression of the chronic neurodegenerative disease.
Another hope is that the discovery, reported in Translational Psychiatry, may lead to new avenues for diagnosing Alzheimer’s, for instance through a blood test.
Amyloid- becomes toxic when a misfolded version is formed, which can induce other amyloid- proteins to misform, in a sort of chain reaction. That first misfolded version is called a seed and once you have a lot of them, you get amyloid plaque.
For what it's worth, science still doesn't know what properly folded amyloid- does.
Not even the role of the plaques entirely clear. Until now, Alzheimer’s research has centered on two specific pathological hallmarks of disease: deposits of misfolded amyloid- peptide plaques, and the nerve tangles found in diseased brains, explains Dr. David Gurwitz said. There's a snag though: "Recent studies suggest amyloid- plaques are also a common feature of healthy older brains," says the doctor, which begs questions about the role of amyloid- peptides in Alzheimer's disease pathology.”
The blood test becomes feasible given the observation that reduced expression of RGS2 is already noticeable in blood cells during mild cognitive impairment, the earliest phase of Alzheimer’s, says Gurwitz. “This supported our theory that the reduced RGS2 expression represents a ‘protective mechanism’ triggered by ongoing brain neurodegeneration,” he adds.
The team further found that the reduced expression of RGS2 was correlated with increased amyloid- neurotoxicity. It acted like a double-edged sword, allowing the diseased brain to function with fewer neurons, while increasing damage to it by accumulating misfolded A.
“Several genes and their protein products are already known to be implicated in Alzheimer’s disease pathology, but RGS2 has never been studied in this context,” Gurwitz said. “We now propose that whether or not A is a primary culprit in Alzheimer's disease, neuroprotective mechanisms activated during early disease phases lead to reduced RGS2 expression.”
The research was led by Dr. David Gurwitz of the Department of Human Molecular Genetics and Biochemistry at TAU’s Sackler School of Medicine and Prof. Illana Gozes of Tel Aviv University's School of Medicine.