MDNews - Greater Boston

One Step Ahead: Revolutionary Blood Test Could Help Identify Alzheimer's Years in Advance By Laura Ward NEW RESEARCH CONDUCTED BY THE MAYO CLINIC FOCUSES ON EARLY MECHANISMS THAT UNDERLIE THE DISEASE PROGRESSION OF ALZHEIMER'S DISEASE. S PORADIC ALZHEIMER'S DISEASE accounts for nearly 95 percent of all diagnosed cases, yet its cause remains widely unknown. Researchers at the Mayo Clinic are working to develop a breakthrough test that could potentially reveal distinct metabolic signatures in blood plasma that are related to the disease. "We know that pathophysiological changes associated with Alzheimer's disease begin at least 10 to 25 years before dementia onset," explains Eugenia Trushina, PhD, Assistant Professor in the Department of Neurology and the Department of Pharmacology and Experimental Therapeutics at the Mayo Clinic. "In our laboratory, we began by using cellular and animal models to understand early molecular mechanisms of Alzheimer's disease. Among our previous observations was the notion that mitochondrial dynamics and function were affected early in the disease, contributing to further neuronal dysfunction." On the Path to Discovery Initially, Trushina and her colleagues applied metabolomic profiling to detect changes in core metabolic pathways related to mitochondrial dysfunction using transgenic animal models. 18 | Greater Boston MD NEWS I MDNEWS.COM "These changes in the core metabolic pathways confirmed that mitochondrial dysfunction preceded the onset of memory phenotype and amyloid plaque formation in three mouse models of familial Alzheimer's disease," says Trushina. "The results encouraged us to conduct studies in human patients, applying a similar approach to examine whether changes in mitochondrial function are also associated with disease progression in humans." Using a similar metabolomic approach to that of animal models, Trushina examined changes in metabolites found in the cerebrospinal fluid and plasma from test patients with early Alzheimer's disease. "Given the considerable parallel between mouse and human metabolism, the use of metabolomics provides ready translation of animal research into human studies for accelerated drug design," Trushina explains. "Therefore, we are very interested in this application since metabolomics could help to monitor the efficacy of novel therapeutic approaches in the animal model of disease and also could be used to do the same in humans." More to Come Because Alzheimer's disease is highly complex, affecting multiple pathways within the brain, it is often too late to "fi x" the problem by the time a patient is diagnosed, Trushina says. "We hope our research helps develop tests for an early diagnosis testing model that would aid in the development of drugs targeting early pathways," she concludes. I

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