Brain Genes Can Go Bad Early

Finding could lead to early detection, prevention

WEDNESDAY, June 9, 2004 (HealthDayNews) -- Some genes in brain cells involved in basic thinking functions begin to go bad as early as middle age, says a new study that opens the way to a better understanding of age-related mental conditions such as Alzheimer's disease.

The study looked at the pattern of gene expression in 30 postmortem brain tissue samples from individuals as young as 26 and as old as 106. It found the degeneration often begins at age 40.

"We found a set of genes whose expression changed significantly as a function of aging," said study author Dr. Bruce A. Yankner, a professor of neurology at Children's Hospital Boston. "These genes include those that play a role in synaptic plasticity, the ability of brain cells to form new connections and to strengthen or weaken existing connections."

The finding is "a first step in the application of genomic technology to what it is that happens in the brain that causes cognitive changes in aging," Yankner said. The ultimate goal of the research is to identify individuals whose brain cells are particularly vulnerable to damage and to prevent or reverse the damage, he said. The report appears in the June 10 issue of Nature.

"We could use our model system to determine whether these changes in the aging brain give rise to Alzheimer's disease," Yankner said. "Some brains compensate for the damage better than others. If we understood the interface between normal and diseased cells, we might be able to intervene early."

The study used a sophisticated screening technique called transcriptional profiling that can evaluate the function of thousands of genes at a time. It found the expression of genes that play a role in learning and memory was significantly reduced in older brains.

All genes are vulnerable to damage caused by environmental pollutants and fast-reacting molecules called free radicals, Yankner said, but the vulnerability appears to be greater in some individuals.

"We would like to be able to genetically identify those who are likely to develop damage and prevent it," he said.

It is a "provocative" study, said Zaven Khachaturian, senior science advisor to the Alzheimer's Association, but there are some drawbacks to it.

One is the relatively small number of brains that were examined, he said: "For the conclusions to be valid, you need a much larger number of subjects."

Another problem is that "there is no information about the cognitive ability of the individuals involved," said Khachaturian. That information would link the changes in gene expression to mental function.

Nevertheless, the study "is giving us some clues of what to look for," he said. "It might be a hypothesis-generating kind of study. We could use the results to explore further."

One possible study would compare gene function in 20-year-olds with memory problems and those without such problems, Khachaturian said. "Then you could look at 100-year-olds and see if the findings hold up," he explained.

More information

You can keep abreast of the latest work on Alzheimer's disease by consulting the Alzheimer's Association.

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