Protein Levels in Spinal Fluid May Spot Alzheimer's

Study Suggests Potential for New Test to Detect Early Alzheimer's Disease

By Salynn Boyles
WebMD Health News

Reviewed by Laura J. Martin, MD

June 22, 2011 -- High levels of a protein in the spinal fluid of older people with mild memory loss may help predict which patients will develop Alzheimer's disease, a study shows.

The study by researchers at Germany's Technical University Munich looked at levels of amyloid precursor protein (APPB) in patients with mild cognitive impairment (MCI), a condition indicating some memory problems but not enough to be classified as dementia. The researchers found that high levels of APPB were linked to the patients' later development of Alzheimer's.

Predicting Alzheimer's Disease

Elevated AAPB in combination with elevated tau protein, which indicates brain cell damage, was roughly 80% accurate in predicting Alzheimer's disease progression in elderly patients who entered the study with mild cognitive impairment (MCI).

If the findings are confirmed, cerebrospinal fluid APPB could help identify patients who will benefit from emerging Alzheimer's treatments very early in the course of their disease, study researcher Robert Perneczky, MD, tells WebMD.

"With a little luck we will have effective disease-modifying therapies for Alzheimer's disease in just a few years," he says. "These treatments will have the greatest benefit for patients who start them very early in the disease process, and we need effective biomarkers to identify these patients."

About 15% of older patients with a diagnosis of mild cognitive impairment (MCI) will progress to Alzheimer's disease over the course of a year.

But some patients never progress, and others experience improvements in memory.

Testing Biomarkers

Established biomarkers help distinguish Alzheimer's disease from other causes of memory decline, such as depression, but they have not proven very useful for predicting progression to Alzheimer's in people with few symptoms, Perneczky says.

In their effort to determine if amyloid precursor protein improves the predictive ability of the established biomarkers, Perneczky and colleagues took samples of cerebrospinal fluid from 58 patients with mild cognitive impairment and then followed the patients for three years.

The fluid was tested for levels of APPB, as well as tau protein and other markers.

During the follow-up, 21 study participants developed Alzheimer's disease, 27 retained the diagnosis of MCI, and eight patients experienced improvements in memory.

The average APPB levels for patients who progressed to Alzheimer's were significantly higher than for patients who did not progress.

The best predictor of whether an MCI patient would develop Alzheimer's was that patient's age, combined with tau protein and APPB levels.

When these three factors were combined, the results were roughly 80% accurate in predicting progression to Alzheimer's disease.

The study appears in the June 22 online edition of the journal Neurology.

"This is clearly better than what we have seen with the established biomarkers," Perneczky says, adding that the next step is to confirm the findings and determine if APPB is useful for predicting cognitive decline in healthy older people with no evidence of memory decline.

If future trials prove promising, spinal taps may become a routine screening test for older people to identify those at risk for developing Alzheimer's long before memory loss occurs, neurologist Roger N. Rosenberg, MD, tells WebMD.

Rosenberg directs the Alzheimer's Disease Center at the University of Texas Southwestern Medical Center.

"It may be fair to say that we can't really treat Alzheimer's," he says. "The hope is that we will be able to treat those at risk to prevent the cognitive declines from happening, but we have to identify them first."



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SOURCES: Perneczky, R. Neurology, June 22, 2011.Robert Perneczky, MD, department of psychiatry and psychotherapy, Technical University Munich, Germany.Roger N. Rosenberg, MD, director, Alzheimer's Disease Center; professor of neurology, University of Texas Southwestern Medical Center.News release, American Academy of Neurology. ©2011 WebMD, LLC. All Rights Reserved.