28 Sep 2012

Microchimeras—cells from another individual, commonly a fetus—have been detected in many human organs, but never before in the brain. Now, researchers led by Lee Nelson at the University of Washington, Seattle, report finding male DNA in women’s brain tissue taken on autopsy. Writing in the September 26 PLoS One, first author William Chan and colleagues reveal that women who had this microchimerism were less likely to have died with Alzheimer’s disease. Nelson did not want to speculate on what that means for women’s risk of developing AD, but noted other studies have suggested microchimerism protects against certain autoimmune diseases.

Maternal microchimerism occurs when cells from the mother make their way into the fetus. The opposite also occurs. Babies' cells can end up in the mother, where they continue to survive long after pregnancy. Fetal microchimerism has been detected in women’s thyroids, lungs, skin, and other organs. Nelson wondered if fetal cells can pass the mother’s blood-brain barrier and wander into the brain, and if so, how long they may persist there. To answer that, the researchers examined autopsy samples from 59 women who died between the ages of 32 and 101. They obtained tissue samples from the University of Washington, and also from the Harvard Brain Tissue Resource Center at McLean Hospital in Belmont, Massachusetts. According to the National Institute on Aging/Reagan Institute criteria for AD pathology, 33 of the women had had that disease.

Using DNA amplification to test for the male-specific, Y chromosome gene DYS14, Chan found that 37 (63 percent) of the women harbored male DNA in their brains. “We were surprised at the extent,” Nelson told Alzforum. “We expected we might find it [microchimerism], but didn’t expect it to be this frequent or present in most [brain] areas.” The researchers found the male gene in the neocortex, hippocampus, cerebellum, and spinal cord. Intriguingly, subjects who’d had AD tended to have more male DNA. The odds of a tissue sample with the microchimerism also testing positive for AD pathology was 60 percent less than for DYS14-negative samples. However, one subject who died without any signs of neurologic disease and who had 10-fold more male DNA in her brain than any of the others skewed the analysis. “We need to look at many more samples to come to any firm conclusions,” said Nelson.

This is not the first time pregnancy has been associated with Alzheimer’s. Previous work suggests that AD risk increases with the number of pregnancies (see Colucci et al., 2006). In this study, the authors had no access to pregnancy history. Nelson said that it is unclear how pregnancy or microchimerism might impact AD risk. She said for rheumatoid arthritis, pregnancy seems to be protective against it for most women. For others, it seems to increase the risk. “This could be because they received cells from the fetus that are genetically predisposed to the disease. It’s like a mini-gene transfer,” she said.

The extent and form of the microchimerism could be important, too. In this latest work, the amount of male DNA in the brain tissue equated to about 0.5 percent of the total. Whether that can influence disease risk may depend on where it occurs. By fluorescence in-situ hybridization, Chan found that the DNA is in cells. What kind of cells remains to be seen, but Nelson noted that in mice, fetal cells can make their way into the maternal brain and eventually become neurons (see Zeng et al., 2010).—Tom Fagan