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Can These 'Fingerprints' Identify Alzheimer's Disease

January 4, 2007
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Scientists collaborating at Cornell University in Ithaca and Weill Cornell Medical College in New York City have identified a panel of 23 protein biomarkers in cerebrospinal fluid that acts as a neurochemical "fingerprint," which doctors might use someday to identify patients living with Alzheimer's disease.

The research is published in the online edition of the journal Annals of Neurology.

Right now, physicians rely on their clinical judgment to decide whether a particular patient has Alzheimer's, rather than some other form of dementia. In many cases, the diagnosis remains uncertain until brain tissue is examined at autopsy.

According to Kelvin Lee, the Samuel C. and Nancy M. Fleming Professor of Molecular and Cell Biology and associate professor of chemical and biomolecular engineering at Cornell: "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. Those postmortem tests confirmed that the panel is over 90 percent sensitive in identifying people with Alzheimer's disease."

Researchers at a variety of centers have long sought biomarkers in blood or cerebrospinal fluid that identify the presence of Alzheimer's pathology, 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 Norman Relkin, M.D., associate professor of clinical neurology and neuroscience at Weill Cornell, and director of the Memory Disorders Program at New York-Presbyterian Hospital/Weill Cornell Medical Center.

Erin Finehout, Ph.D., the lead author on the research who had been a doctoral student in Lee's laboratory, said that this has great potential to affect human health.

"Typically, Alzheimer's disease is not diagnosed until the disease has already caused some amount of dementia," she said. "Having a chemical test available may allow patients to be diagnosed earlier in the course of the disease."

"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," said Lee.

"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," said Relkin.

For example, some of the biomarkers are associated with proteins that clog the brains of Alzheimer's patients. Other molecules were linked to inflammation, also a part of Alzheimer's brain pathology.

Still other proteins in the panel were linked to synaptic dysfunction -- the breakdown of communication between brain cells that occurs as Alzheimer's disease progresses.

"A subsequent validation group of 10 patients with suspected Alzheimer's, and 18 healthy and demented control subjects, turned up similar results," stated Relkin.

"Based on their clinical symptoms, we found the new screen to have 93 percent sensitivity to probable cases of Alzheimer's and a 90 percent accuracy in avoiding false diagnoses," concluded Ralkin.

Despite their excitement over the new findings, the researchers stress that the results still need to be replicated in much larger populations.

 

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