In a recent study scientists have discovered that an inflammatory immune protein is much more common in the brains of women with Alzheimer’s, offering a hint as to why women are more susceptible to the condition than men.
As part of the Mechanistic insight into female predominance in Alzheimer’s disease based on aberrant protein S-nitrosylation of C3 study, scientists from Scripps Research and Massachusetts Institute of Technology (MIT) used methods to detect S-nitrosylation, which can modify a protein’s function, to quantify proteins modified in 40 postmortem human brains.
Half of the brains examined were from people who had died of Alzheimer’s, while the other half were from people who hadn’t with each group divided equally between males and females.
In the brains affected by Alzheimer’s, the scientists found 1,449 different proteins that had been modified by S-nitrosylation.
Among the proteins modified the most in this manner, there were several associated wit Alzheimer’s, including complement C3, with the levels of S-nitrosylated C3 (SNO-C3) more than six-fold higher in female Alzheimer’s brains compared to male Alzheimer’s brains.
Why are women at greater risk of #Alzheimers? Prof. Stuart Lipton & @MIT discover harmful form of an inflammatory immune protein called complement C3 present at higher levels in brains of women who had died with the disease compared to men https://t.co/hYz3EEwc0D @ScienceAdvances pic.twitter.com/bUdO5chxn2
— Scripps Research (@scrippsresearch) December 14, 2022
Study senior author Stuart Lipton, MD, PhD said the “new findings suggest that chemical modification of a component of the complement system helps drive Alzheimer’s, and may explain, at least in part, why the disease predominantly affects women.”
“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 said.
Previous studies have offered some insight as to why SNO-C3 is more common if female brains, with evidence pointing to the female hormone estrogen which has protective properties for the brain.
Researchers hypothesised that the protective properties are reduced when estrogen levels drop with menopause.
The study, published in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association, was conducted by researchers at the School of Public Health, Boston University School of Medicine (MED), and the University of Chicago who identified a connection between a protein-coding gene called MGMT and an increased risk of Alzheimer’s disease in women.
As part of the study, researchers conducted a genome-wide association study (GWAS) for Alzheimer’s in two independent datasets using different study approaches.
In a new study published in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association, researchers have identified a novel #gene called MGMT that increases the risk of #Alzheimer’s disease in #women. https://t.co/Ck9tHZSgdv
— NeuronUP EN (@NeuronupEN) July 7, 2022
One approach analysed dementia in a large extended family of Hutterites, who are a population of central European ancestry who due to their isolated culture and small gene pool, are often studied for genetic determinants of disease. The individuals in this first approach of the study were all women with Alzheimer’s.
The second approach analysed data from a group of 10,340 women who had reduced levels of APOE ε4, a gene considered to hold a strong link to the development of Alzheimer’s in those aged over 65.
Researchers found a significant association between MGMT and the development of Alzheimer’s Disease.
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