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Dr Christophe de Jaeger (Longevity and geriatrics)
American scientists have revealed a new molecular cause of Alzheimer’s disease. This discovery could also explain why women are more at risk of contracting the disease. They now represent nearly two-thirds of cases.
Faced with the mysteries that still surround Alzheimer’s disease, research is progressing. A few weeks after the encouraging results on a first treatment, a new study published on December 14, 2022 by the Massachusetts Institute of Technology (MIT) could explain the inequality between men and women in the face of this disease.
Alzheimer’s: women represent two thirds of cases
Alzheimer’s disease is the most common form of dementia. It occurs with aging, and is always fatal, usually within a decade of its onset. There is no approved treatment that can halt the disease process, let alone reverse it.
Why ? Mainly because scientists have failed to elucidate the development of this pathology. Scientists also don’t know why women account for nearly two-thirds of cases. But a team from MIT is advancing a new hypothesis.
In this study, published in Science Advances, researchers looked at 40 brains from both men and women. Half came from people who died of Alzheimer’s disease.
The tests revealed 1,449 different types of proteins in the brain that appear with age – several of which had previously been linked to Alzheimer’s disease. Scientists were particularly interested in proteins resulting from a specific chemical reaction (S-nitrosylation) capable of causing inflammation and inappropriate immune reactions in the brain.
One protein caught their attention: the protein known as SNO-C3 (resulting from the transformation of a harmless C3 protein into SNO-C3 by S-nitrosylation). According to the researchers, proteins like SNO-C3 can activate brain immune cells called microglia capable of destroying synapses, the connection points through which neurons send signals to each other. And this destruction of synapses could at least partly explain the occurrence of Alzheimer’s disease.
These tests revealed that levels of SNO-C3 were six times higher in the brains of women with Alzheimer’s disease than in men.
Why are women more exposed?
But why is SNO-C3 more common in the brains of sick women? Researchers hypothesize that estrogen specifically protects women’s brains from the chemical reaction that will “hijack” C3 – and this protection disappears as estrogen levels drop sharply with menopause. Experiments on human brain cells in culture would confirm this theory.
Bottom Line: Estrogen acts as a natural anti-inflammatory and is thought to play a role in suppressing SNO-C3. While sex hormone levels in men increase with age, estrogen drops sharply in women during menopause.
“Why women are more susceptible to Alzheimer’s disease has long been a mystery, but I believe our findings represent an important piece of the puzzle that mechanistically explains women’s increased vulnerability as they age,” said De Stuart Lipton, urologist and author of the study.
“Our new findings suggest that chemical modification of a component of the complement system promotes the occurrence of Alzheimer’s disease and may explain, at least in part, why the disease predominantly affects women.”
Estrogens, the key to protection against Alzheimer’s?
For Christophe de Jaeger, a geriatrician and French researcher in the aging of the human body, the study is fascinating but requires further investigation:
“In Alzheimer’s disease, the etiology and etiopathogenesis are still poorly understood, and lead to few therapeutic possibilities to date. There are a multitude of avenues: environmental genetics, hormonal, deficiency, infectious… In this article, the researchers address the anomalies of energy management within cells and the problem of neuro-inflammation which can be a cellular mechanism. They evoke in this way the problem of estrogens which fall at menopause. It is a 20-year-old theory, recently put forward according to which estrogens would have an interest in the treatment of neurodegenerative pathologies. This study demonstrates that estrogen can alter nitric oxide metabolism. By confirming this discovery, these researchers are now providing a new physiopathological lead and therefore a new treatment lead”.