Modified immune protein, which harms brain connections, is much more common in the brains of women with Alzheimer’s compared to men, according to a study published in Science Advances.
Women account for nearly two-thirds of Alzheimer’s cases. Despite this disparity, scientists do not fully understand why women are at a higher risk of developing this disease.
Scientists at Scripps Research and the Massachusetts Institute of Technology (MIT) have discovered a clue that may explain why women are at a greater risk for Alzheimer’s. The researchers’ findings may partly explain why the disease predominantly affects women.
The study revealed that a harmful, chemically modified form of an inflammatory immune protein known as complement C3 was present at much higher levels in the brains of women who died from Alzheimer’s disease than in men who died from Alzheimer’s. They also found that estrogen has a protective effect in women, as it protects against the creation of complement C3. However, this hormone drops in production during menopause.
In these brains, the scientists found that 1,149 different proteins have been modified by a process known as S-nitrosylation. Previous research has tied S-glycosylated proteins to Alzheimer’s, including complement C3 (SNO–C3). However, one striking result of this study was that the levels of this modified protein were more than sixfold higher in female Alzheimer’s brains compared to male Alzheimer’s brains.
The researchers hypothesize that estrogen may be a reason for this increase in the presence of modified protein (SNO–C3) in female brains with Alzheimer’s. According to the researchers, estrogen specifically protects women’s brains from C3-S-nitrosylation. However, this protection is lost as women age, as estrogen levels decline sharply with menopause.
“Why women are more likely to get Alzheimer’s has long been a mystery, but I think our results represent an important piece of the puzzle that mechanistically explains the increased vulnerability of women as they age,” Lipton says.
Source: Science Daily