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Study boosts confidence in potential screening tool for Alzheimers disease

ol subjects and measured CSF levels of the suspect protein fragments. As the fluid that bathes the brain, CSF has long been considered the most reliable window available into a living human's neurochemical activity. Beta-amyloid levels in Alzheimer's patients averaged only 183 picograms per milliliter of CSF, compared to 491 in controls. Patients' tau levels dwarfed controls 587 to 224 picograms per milliliter. These differences remained significant even after statistical analysis controlled for effects of age and sex. Taken together the two markers distinguished clinically diagnosed Alzheimer's patients from controls with a sensitivity of 92 percent and a specificity of 89 percent.

Years of education were associated with lower CSF tau levels among Alzheimer's patients, suggesting a possible protective factor. Evidence suggests that the changes in beta-amyloid and tau levels may be present early in the disease process.

The researchers also performed a meta-analysis of 51 similar studies, totaling 3133 Alzheimer's patients and 1481 controls. These included 17 controlled studies of beta-amyloid winnowed from 188 articles, and 34 studies of tau, sifted from an initial list of 200 articles. Of the beta-amyloid studies, 14 of the 17 found the same pattern seen in the NIMH sample. All of the tau studies showed the same pattern as the NIMH sample.

However, for both measures, the researchers found considerable overlap in levels between the Alzheimer's and control groups. "It is evident that the diagnostic sensitivity and specificity of these individual CSF beta-amyloid and tau assays is simply not sufficient to warrant general clinical use of these biomarkers for individual use," they caution. They call for additional studies to standardize assay methodology, and for "real world" comparisons between Alzheimer's patients and people with other forms of dementia, noting that these would likely show even more overlap.

"Perhaps the
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
22-Apr-2003


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