Gene, Linked for 1st Time to Alzheimer’s, May Lead to Blood Test of Susceptibility

Researchers have identified a new gene, called Rgs2 (Regulator of Protein Signaling 2), whose expression levels may be used in future diagnostic blood tests for early detection of Alzheimer’s disease (AD). It is the first time that this gene is implicated in AD.

The study, “RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer’s disease: genome-wide transcriptomic profiling and bioinformatics data mining,” published in the journal Translational Psychiatry, may also lead to new treatments, as Rgs2 expression levels suggested a sensitivity to the more toxic effects of plaque deposits in the brain.

Amyloid-beta plaque deposits are regarded as a key step in the development of Alzheimer’s. How these plaques contribute to disease pathology still raises doubts, however, as plaque deposits are also found in in vivo brain images of elderly people without signs of dementia.

Previous studies have suggested that amyloid-beta brain deposits may constitute, per se, a feature of an aging brain, but certain individuals may be more susceptible to the toxic effects of accumulated deposits than others.

“Alzheimer’s researchers have until now zeroed in on two specific pathological hallmarks of the chronic neurodegenerative disease: deposits of misfolded amyloid-β (Aβ) peptide plaques, and phosphorylated tau protein neurofibrillary tangles found in diseased brains,” one of the study’s lead authors, Dr.  David Gurwitz of the Department of Human Molecular Genetics and Biochemistry at the Sackler School of Medicine at Tel Aviv University, said in a press release.

“But recent studies suggest amyloid-β plaques are also a common feature of healthy older brains. This raises questions about the central role of Aβ peptides in Alzheimer’s disease pathology.”

In this study, researchers tried to identify genes that could be used as markers to predict an individual’s sensitivity to amyloid-beta. To this end, they employed a genome-wide transcriptomic strategy using blood-derived cell lines from healthy individuals and AD patients. This strategy consists in analyzing on a global scale how gene expression changes under different conditions.

The analysis revealed a particular gene, called RGS2, whose expression changed significantly. Specifically, researchers found that in AD patients, the expression of RGS2 was significantly lower than in healthy controls, and that low levels of RGS2 increased the sensitivity of patients’ cells to the toxic effects of amyloid-beta. Moreover, researchers found that RGS2 expression correlated with AD patients’ cognitive function.

“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,” Dr. Gurwitz said. “We now propose that whether or not Aβ is a primary culprit in Alzheimer’s disease, neuroprotective mechanisms activated during early disease phases lead to reduced RGS2 expression.”

In other words, lower expression of RGS2 correlated with increased amyloid-beta neurotoxicity. These results suggest that in the future, potential blood tests measuring RGS2 expression levels may be used as diagnostic tools.

“Our new observations must now be corroborated by other research groups,” Dr. Gurwitz concluded. “The next step will be to design early blood diagnostics and novel therapeutics to offset the negative effects of reduced expression of the RGS2 protein in the brain.”