Genetic Contributor to Alzheimer’s Identified

January 15, 2017

A new Tel Aviv University study identified a gene coding for a protein that turns off neurotransmission signaling, which contributes to Alzheimer’s disease (AD). The gene, called RGS2 (Regulator of Protein Signaling 2), has never before been implicated in AD. The study, published in Translational Psychiatry, may lead to new avenues for diagnosing Alzheimer’s disease—possibly a blood test—and new therapies to halt the progression of the disease. 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.

“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,” Dr. Gurwitz said. “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.”

The researchers pinpointed a common suspect—the RGS2 gene—by combining genome-wide gene expression profiling of Alzheimer’s disease blood-derived cell lines with data-mining of previously published gene expression datasets. They found a reduced expression of RGS2 in Alzheimer’s disease blood-derived cell lines and then validated the observation by examining datasets derived from blood samples and post-mortem brain tissue samples from Alzheimer’s patients.

“We found that reduced expression of RGS2 is already noticeable in blood cells during mild cognitive impairment, the earliest phase of Alzheimer’s,” Dr. Gurwitz observed. “This supported our theory that the reduced RGS2 expression represents a ‘protective mechanism’ triggered by ongoing brain neurodegeneration.” The team further found that the reduced expression of RGS2 was correlated with increased Aβ 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 Aβ.

“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.”

Source: Excerpt of article by Tel Aviv University

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