Protein fingerprinting technique may identify patients at earliest stage of HIV-associated dementia

The technique of proteomics fingerprinting, which generates a profile of proteins found in the blood, indicates that patients with HIV-associated dementia have a different profile than patients without symptoms of dementia, according to an article in the June 24th issue of Neurology. The findings suggest that it may become possible to screen HIV-infected patients for the first signs of cognitive impairment.

"Characterizing dementia in this way is a very new and exciting approach," said senior author Loyda Melendez, Ph.D. "It's a ways off, but our research tells us that we might eventually be able to use a blood test to look for signs of HIV-associated dementia."

Statistics show that roughly 10 to 15 percent of HIV-infected people eventually develop HIV-associated dementia, which causes loss of memory and cognitive skills. Patients also may have motor deterioration, changes in their behavior and personality, or both.

The mechanism underlying develop of the dementia is not understood. In the current study, researchers tested a unique hypothesis that HIV-infected monocytes in the central nervous system may release substances that damage neurons.

Melendez and her colleagues developed a cohort aged 21 to 45 years that included 9 HIV-infected women with moderate to high cognitive impairment, 12 HIV-infected women without evidence of dementia, and 10 women who were not infected with HIV and had no cognitive impairment. All participants underwent complete neurological testing and gave blood samples for testing.

A collaborating research team used a technique known as proteomics, which maps out patterns of activity for particular groups of proteins, to establish a protein fingerprint for each patient. Proteomic analysis showed that of the 177 proteins examined in the study, 38 proteins exhibited different activity levels in patients with HIV-associated dementia than in the 2 groups of women without dementia. All of the patients with the distinct protein pattern had the dementia, but not every woman with dementia shared the profile.

Studies need to be done to more fully describe the protein
profile for HIV-associated dementia, said coauthor Howard Gendelman, MD. "Our results are encouraging, but proteomics is still in its infancy. We've taken the first step in a very long journey to find better ways to diagnose HIV-associated dementia and other diseases."

The researchers have followed the same group of dementia patients and healthy subjects for 1 year, and they plan to continue following them. The investigators also hope to double the number of study subjects in order to improve the statistical significance of their results and to begin including men in the studies.

In addition to continuing their current work, proteomics group plans to purify and sequence the proteins that are altered in patients with dementia and to track protein patterns over time as patients improve or decline clinically.



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