new study We found that altered immune system proteins are more common in women with Alzheimer’s disease (AD) than in men, providing molecular clues as to why women are at higher risk for AD. This research scientific progress.

Women are at higher risk of AD

Alzheimer’s disease, the most common form of dementia, is an age-related progressive syndrome that leads to cognitive decline, 60-70% of dementia cases. Memory, reasoning, and understanding are all affected, along with changes in mood, personality, and behavior.

Although the exact process by which AD develops is not fully understood, Distinctive by aggregation of misfolded amyloid-β protein, abnormal tangles of tau protein, and loss of neural connections (synapses) associated with cognitive decline. no effective treatment It can be used to prevent progression of AD. ~of6 million Americans have AD, most two-thirds Scientists don’t know exactly why this is the case, but women.

and previous research, researchers studied a protein modification process called S-nitrosylation (SNO) that can alter protein function. These so-called ‘SNO proteins’ are involved in the development of several neurodegenerative diseases.

In the current study, researchers investigated the appearance of SNO protein in postmortem brain samples from patients with AD and those without AD and found sex-dependent differences in the appearance of SNO protein in patients with the disease.

Is it due to low estrogen?

The researchers examined postmortem brain samples from 20 patients who died of AD and 20 who did not. The number of men and women per group was the same. Across the cohort, they analyzed the presence and abundance of her SNO proteins and identified nearly 1,500 different types. They found that the addition of SNOs to an immune system protein called complement C3 occurred more frequently in the brains of women with AD than in men.C3 is part of the innate immune system called the complement cascade. It is known to function, be elevated in AD brain tissue, and promote inflammation. The complement cascade can trigger microglia, immune cells resident in the brain, to disrupt synapses, critical signaling, and connections between neurons.

Investigating why the brains of women with Alzheimer’s disease have higher levels of SNO-C3 compared to men, the researchers hypothesized that there might be a relationship with estrogen loss. Cerebral protective properties – Postmenopausal. Experiments with brain cells cultured in the laboratory have confirmed that when estrogen levels fall, SNO-C3 levels subsequently rise, leading to synaptic disruption by microglia.Synaptic loss and cognitive function in AD. Given the correlation with decline, this was an important finding.

“Many previous studies have shown that estrogen may play a role in neurodegenerative diseases such as Alzheimer’s disease, and inflammation has also been linked to the disorder,” he explained. stuart liptonProfessor of Neuroscience at Scripps Research and senior author on this study. “We put him two and two together and identified one of the key players him in the process. That’s SNO-C3.”

Potential Pieces of the AD Puzzle

Nevertheless, Lipton expanded some of the limits of research. Nevertheless, our human stem cell-derived model system shows that SNO-C3 can be involved in impaired synaptic connections between neurons, perhaps best correlated with cognitive decline in Alzheimer’s disease and other dementias. doing. ”

The authors explained that, overall, these findings may provide clues to solving the mystery of why women are more likely to develop AD. We plan further experiments to test whether the compounds have beneficial effects in animal models of AD.

reference: Yang H, Oh C, Amal H, Wishnok JS, et al. Mechanistic insights into female dominance in Alzheimer’s disease based on aberrant protein S-nitrosylation of C3. scientific advantage2022. Doi: 10.1126/sciadv.ade0764

Professor Stuart Lipton was talking to Sarah Whelan, Science Writer at Technology Networks.