December 19, 2006
Researchers have identified a group of proteins in the spinal fluid that may be unique to Alzheimer's disease. The 23 proteins might serve as a unique "fingerprint that could one day lead to a test to diagnose Alzheimer's in people living with the memory-robbing ailment.
Today, doctors must rely on their clinical assessment of memory loss and other symptoms to decide whether a person has Alzheimer's disease rather than some other form of dementia. In many cases, the diagnosis remains uncertain until after death, when an autopsy and analysis of the brain can be performed. A blood test or other test to diagnose Alzheimer's at an earlier stage could be important as new drugs and other therapies that combat, or even reverse, the illness become available. Such a test might also allow doctors to monitor people with the disease to determine whether certain treatments are working.
In the study, scientists at Cornell University and Weill Cornell Medical College in New York used cutting edge "proteomics" technology, which analyzes proteins in the cerebrospinal fluid that bathes the brain and spinal cord. Using detailed image analysis and complex computer and statistical analyses, they compared 2,000 proteins from 34 patients with autopsy-proven Alzheimer's disease to those of 34 age-matched controls without the disease.
"Our study is the first to use sophisticated proteomic methods to hone in on a group of cerebrospinal fluid biomarkers that are specific to autopsy-proven Alzheimer's disease," says Professor Kelvin Lee of Cornell University in Ithaca. "Those postmortem tests confirmed that the panel is over 90 percent accurate in identifying people with Alzheimer's disease." Their findings were published in the December 12 online issue of the Annals of Neurology.
Researchers at a variety of medical centers have long sought markers in the blood or spinal fluid that would provide a test to identify Alzheimer's disease and distinguish it from other conditions that cause dementia. "Some of these studies have met with limited success, but most have correlated their findings with patient's clinical symptoms rather than working with the gold-standard of autopsy-proven Alzheimer's," notes Dr. Norman Relkin of Weill Cornell Medical College, who worked on the current study.
"Just as the human genome reflects the array of genes a person possesses, the 'proteome' is the vast collection of proteins expressed by those genes," Dr. Lee explains. "Essentially, we used high-tech methods to contrast the proteomes of Alzheimer's patients against those of a control cohort that included people with other forms of dementia as well as healthy individuals, looking for key differences between the two groups."
This effort yielded intriguing results: 23 proteins that individually might not point to Alzheimer's but together formed an identifying pattern or "fingerprint" specific to the illness. "Although it need not have turned out that way, several of the 23 markers that emerged from this analysis proved to be proteins with known links to the pathological mechanisms of Alzheimer's disease." Dr. Relkin says.
For example, some of the markers included proteins associated with beta-amyloid, the toxic protein that builds up in the brains of those with Alzheimer's disease. Others were linked to inflammation, which doctors increasingly believe plays a role in Alzheimer's, heart disease, and other ills of aging. Still other proteins in the "fingerprint" were linked to problems in the communication between brain cells that occurs as Alzheimer's disease progresses.
The researchers are currently using the tests to monitor experimental treatments that may have an impact on the underlying disease process. "You might have a promising treatment for the disease, but how can you know for sure that it's impacting on the underlying pathology, rather than just easing outward symptoms, as most of the drugs that we have now do?" Dr. Relkin says. "We are hopeful that by monitoring changes in these cerebrospinal biomarkers, we can actually track the effectiveness or lack thereof of experimental drugs."
The researchers are currently using the protein "fingerprint" to study the effects of an experimental treatment for Alzheimer's called IVIg, for intravenous immunoglobulin. Dr. Relkin notes that early data suggest that IVIg may be having a positive impact on the underlying disease process.
Despite their excitement over the new findings, the researchers stress that the results still need to be replicated in much larger groups of people. One such study at multiple medical centers is currently under way.
To keep informed about current developments in Alzheimer's diagnosis and treatment, visit www.ALZinfo.org. The Fisher Center for Alzheimer's Research Foundation funds critical research into the underlying causes of Alzheimer's and the search for a cure.
Finehout, E. Annals of Neurology, December 2006; vol 60. News release, Cornell University News Service.