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New Discoveries: Alzheimer’s disease

March 5, 2012

(Ivanhoe Newswire)– With the help of mice, researchers have now found that mitochondria in the brain are dysfunctional early on in Alzheimer’s disease, even before memory loss.

The team examined mitochondria in three mouse models, each using a different gene shown to cause familial, or early-onset, Alzheimer’s disease. The specific mitochondria changes corresponded with the mutation type and included altered mitochondrial movement, structure, and energy dynamics. The changes occurred in the brain even before the mice showed any symptoms such as memory loss. The group also found that the mitochondrial changes contributed to the later loss of mitochondrial function and the onset and progression of Alzheimer’s disease.

“One of the most significant findings of this study is our discovery of the impact of mitochondrial dysfunction in Alzheimer’s disease,” Eugenia Trushina, Ph.D., Mayo Clinic pharmacologist and senior investigator on the study, was quoted saying. “We are asking: Can we connect the degree of mitochondrial dysfunction with the progression of symptoms in Alzheimer’s disease?”

With the help of a Mayo researcher Petras Dzeja, Ph.D., the team applied a fairly new method called metabolomics, which measures the chemical fingerprints of metabolic pathways in the cell – sugars, lipids, nucleotides, amino acids and fatty acids.

The researchers hope that the panel of metabolomic biomarkers they discovered can eventually be used for early diagnosis, treatment, and monitoring of Alzheimer’s progression.

“We expect to validate metabolomic changes in humans with Alzheimer’s disease and to use these biomarkers to diagnose the disease before symptoms appear — which is the ideal time to start treatment,” Dr. Trushina was quoted saying.

The researchers examined neurons of three various genetic animal models of Alzheimer’s disease. Researchers applied a mitochondria-specific dye and observed their motion along axons, a process called axonal trafficking. Demonstrating that even in embryonic neurons afflicted with Alzheimer’s disease, well before the mice show any memory loss, mitochondrial axonal trafficking is inhibited. Using a panel of techniques that included electron and light microscopy, they determined that in the brains of mice with Alzheimer’s disease, mitochondria tended to lose their integrity, ultimately leading to the loss of function. Importantly, dysfunctional mitochondria were detected at the synapses of neurons involved in maintaining memory.

“We are not looking at the consequences of Alzheimer’s disease, but at very early events and molecular mechanisms that lead to the disease,” Dr. Trushina was quoted as saying. The next step is looking at the same mitochondrial biomarkers in humans, she says. As the researchers begin to understand more about the mitochondrial dynamics that are altered in Alzheimer’s disease, they hope to move on to designing drugs that can restore the abnormal bioenergetics and mitochondrial dynamics to treat the disease.

SOURCE: PLoS ONE, February 29, 2012




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