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Molecular link found between diabetes and Alzheimer's disease.

SAN DIEGO, Calif, January 8, 2016 -- Investigators here have discovered that high sugar caused by Type 2 (adult-onset) diabetes and the beta-amyloid protein associated with Alzheimer's disease induce the same pathological modification on multiple enzymes in the brain.

The findings help explain the well-known association between Type 2 diabetes and Alzheimer's disease.

The scientists in the Neurodegenerative Disease Center at Scintillon Institute for Biomedical and Bioenergy Research used a "disease-in-a-dish" model to discover molecular pathways that are in common in both diabetes and Alzheimer's.

They genetically reprogrammed the skin of human patients to make induced pluripotent stem cells (iPSCs) used to derive nerve cells. They also used mouse models of each disease to analyze the combined effects of high blood sugar and beta-amyloid protein in living animals.

They found that both excess sugar and beta-amyloid protein caused a rise in nitric oxide and other free radical species. This change led to the modification of multiple enzymes through a chemical process called S-nitrosylation.

Because this modification changes enzymatic activity, it caused abnormal increases in both insulin and beta-amyloid protein. Moreover, the changes in enzyme activity led to damage of synapses, the region where nerve cells communicate with one another in the brain.

The combination of high sugar and beta-amyloid protein caused the greatest loss of synapses. Since loss of synapses correlates with cognitive decline in Alzheimer's, high sugar and beta-amyloid coordinately contribute to memory loss.

This work points to a new common pathway to attack both Type 2 diabetes, along with its harbinger, metabolic syndrome, and Alzheimer's disease. It also means that diseases are related on a molecular basis and can be treated with new drugs on a common basis.

About 40 percent of Americans suffer from metabolic syndrome, characterized by obesity, increased blood pressure, and abnormal handling of sugar. This population may not only be at risk for developing diabetes, but also for developing the symptoms of Alzheimer's disease, known to affect about 5.3 million Americans.

Citation: "Elevated glucose and oligomeric [beta]-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation," Mohd Waseem Akhtar et al., Nature Communications, DOI: 10.1038/ncomms10242

Abstract:/

http://dx.doi.org/10.1038/ncomms10242

Contact: Stuart A. Lipton, slipton@ucsd.edu

Contact: http://www.scintillon.org/

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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Jan 18, 2016
Words:375
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