A drop in estrogen due to menopause could make females more susceptible to a newly identified brain protein – and explain why they’re at higher Alzheimer’s risk than males.
While previous research has shown women are at a higher risk for developing Alzheimer’s (in the US, two-thirds of cases are women) a new study by scientists at Scripps Research and Massachusetts Institute of Technology discovered women who died from Alzheimer’s had a much higher amount of a chemically-modified version of the protein complement C3 in their brains compared to men who died from the disease.
The researchers, whose study was published in the journal Science Advances, believe the post-menopause drop in the hormone estrogen – which they showed normally helps protect against this chemical modification of complement C3 – may leave women more vulnerable to this version of C3.
Study co-author Professor Stuart Lipton told medicalnewstoday.com that complement C3 is a ‘component of a cascade of proteins in the blood that mediate inflammatory infections, usually to fight infections.
‘However, they are also known during development to help sculpt new synapses – the connections between nerve cells that allow them to talk to one another, and are the basis for learning and memory.
‘In disease, excessive activity of complement C3, however, can result in loss of synapses, contributing to dementia.’
Lipton’s team found a chemical reaction called protein S-nitrosylation makes a modified version of complement C3 which is ‘aberrantly activated in Alzheimer’s disease’ and was more than six times higher in female brains with Alzheimer’s than in male brains with Alzheimer’s.
The researchers believe estrogen may also offer protection in the female brain from S-nitrosylation of complement C3 – but this protection diminishes as a person’s estrogen level naturally decreases during menopause.
Professor Lipton summed up: ‘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.’
