"This is the first noninvasive test that can predict a clinical diagnosis of Alzheimer's disease," said Domenico Praticò, MD, assistant professor in Penn's Department of Pharmacology. "Since there is no cure for Alzheimer's disease, physicians could slow the course of the disease if it is caught early enough."
Within four years of initial diagnosis, up to 50% of people with MCI develop Alzheimer's disease. 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.
In the study, published in the June edition of Archives of Neurology, Praticò and his colleagues measured isoprostane in blood and urine samples obtained from 50 patients with a clinical diagnosis of AD, 33 patients with MCI, and 40 healthy volunteers. Two weeks later, a CSF sample and a second urine sample were taken from 28 of the AD patients, 17 of the MCI patients, and 18 of the control subjects. The researchers found significantly higher levels of isoprostane in CSF, blood, and urine of MCI and AD subjects than in the volunteers. Remarkably, the samples taken from the MCI subjects and the volunteers differed only in respect to their isoprostane levels.
"We found that patients with MCI have increased brain oxidative damage before the onset of AD – damage that can be detected in the form of isoprostanes in urine, as this study shows," said Praticò. "In fact, five MCI subjects, all with high isoprostane levels, converted to AD during follow-up."
Patients that are diagnosed with Mild Cognitive Impairment typically present their physicians with persistent memory loss that is not normal for someone of their age and education. Although their memory is impaired, MCI patients are capable of living largely independent lives. At this stage, it is difficult to determine whether a person with MCI will eventually have Alzheimer's or whether they will progress to a form of unrelated dementia.
A urine sample taken in the doctor's office may be a first point of decision in gauging the risk of developing AD. Further tests could then determine the severity of a patient's condition and course of treatment. For example, studies have shown that the transition from MCI to AD occurs fastest in people who have a gene called apoE4 and whose brain's hippocampus region is shown to be smaller as measured in an MRI scan.
"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."
While at the moment this test is not yet clinically available, the team is working on the development of a version of it that could be broadly and easily performed.
Unlike a spinal tap, a urine test is simple to do and provides a painless and noninvasive way of assessing the situation. "The advantages are clear: with an easier test, doctors can diagnose the disease sooner and respond better to the patient's needs," said Praticò.
This research was supported by grants from the National Institutes of Health and the American Heart Association. Trial participants were selected at the Memory Disorders Clinic of Penn's Alzheimer's Disease Center.
Archives of Neurology