Penn researchers find new marker for Alzheimer's disease

November 28, 2000

A simple urine test could make it easier to track and treat the disease

(Philadelphia, Pa.) - Researchers at the University of Pennsylvania Medical Center have determined that a form of isoprostane found in urine could help chart the course of Alzheimer's disease (AD) in victims, allowing doctors to diagnose the disease earlier and treat it more accurately. The isoprostane is one of a family of molecules formed from fat and lipids when they are attacked by free radicals. The amount of isoprostane increases dramatically in the presence of AD and corresponds directly with another well-known AD marker, the tau protein. While an important indicator for AD, the tau protein is only found in the cerebrospinal fluid (CSF), which can only be measured by a lumbar puncture, commonly called a spinal tap. Isoprostanes, however, can be measured in CSF, blood, and urine. "Unlike a spinal tap, a urine test is simple to do and provides a painless and noninvasive way of assessing the situation," said Domenico Praticò, MD, assistant professor of pharmacology at the University of Pennsylvania School of Medicine and lead author of the study. "The advantages are clear: with an easier test, doctors can diagnose the disease sooner, chart its progress more accurately and, in turn, prepare a better course of treatment."

The study, which appears in the November issue of the Annals of Neurology, compared the amount of isoprostane in the CSF, blood, and urine taken from 35 patients with a clinical diagnosis of AD and from 25 healthy volunteers at Penn's Alzheimer's Disease Center. The researchers found that AD patients had higher levels of isoprostane in CSF, blood, and urine when compared to the non-AD subjects. Moreover, these levels directly correlated with the levels of tau protein in AD patients as well as with the results of mental cognitive tests. This development offers a new clinical tool for both physicians and researchers. Physicians have a means for easily detecting AD in at-risk patients, while researchers can use this tool to gain insight into the role of free radicals in AD. As AD progresses, it attacks the brain and causes severe damage in the areas important for memory, judgement, and language. This destruction leads to other clinical complications and, eventually, death.

"One hypothesis is that, in AD, healthy brain tissue is damaged by the local formation of large amounts of free radicals," said Praticò. "Isoprostanes are the byproducts of fats in the human body that were warped by free radical attack. They then accumulate in CSF, blood, and urine as the body works to get rid of them."

In a related study also published in the November issue of Annals of Neurology, Praticò and colleagues determined that isoprostane found in urine could serve as a marker for free radical damage in people suffering from Down's Syndrome. Like AD, free radical damage in the brain is key part of the progress of Down's Syndrome. In fact, Down's Syndrome patients often exhibit AD-like brain lesions in young adulthood. "It is further evidence of the effectiveness of isoprostane as a specific and noninvasive marker for free radical damage in general, and Alzheimer's disease in specific," said Praticò.

Although screening urine for isoprostane levels is not now performed clinically, the researchers hope to simplify the test so that it can be performed easily at hospitals and even physician's offices. For now, Praticò and colleagues plan to repeat the study with patients who exhibit Mild Cognitive Impairment (MCI). Since up to 45 percent of MCI sufferers eventually progress toward a clinical diagnosis of AD, this study will provide added support to the idea that this marker can predict the presence of AD. In addition, the researchers plan to look into the question of how antioxidants might lessen the effects of free radical damage in the brain.
The research was conducted with the cooperation of pharmacology and neurology, in conjunction with the Center for Experimental Therapeutics, Center for Neurodegenerative Disease Research, and Memory Disorder Clinic at the Alzheimer's Disease Center.

Other Penn researchers involved in this study include John Q. Trojanowski, MD, PhD, Christopher M. Clark, MD, and Virginia M-Y Lee, PhD.

University of Pennsylvania School of Medicine

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