Alzheimer's Is More Common in Women, And This May Help Explain Why

In the US, roughly two out of every three people with Alzheimer's is a woman, a statistic that could be partially explained by the fact women typically live longer than men.

Yet researchers have suspected there could be more to the story. Now two new studies raise the possibility of complex interactions between hormones and altered gut microfloa as potential contributing factors.

In a study led by researchers from the University of Chicago, experiments on mice revealed the female hormone estrogen is significantly linked to the build-up of amyloid beta protein clumps in the brain, a key feature of Alzheimer's disease.

When female mice bred to develop an Alzheimer's-like disease had their gut microflora distrupted with antibiotics, their blood estrogen levels shot up.

Furthermore, when estrogen production was prevented in the mice, fewer amyloid deposits were observed in their brain tissues. Changes in the make-up of gut bacteria were also noticed when these ovary-less mice were given an estrogen supplement to restore hormone levels.

Considering the team's previous work showing antibiotics only having an effect on reducing amyloid beta deposits male mice, it appears that estrogen plays a significant role in the mechanisms behind the pathology. Most probably, in combination with the gut microbiome, the mix of microorganisms in the stomach and connected tubing.

"Estrogen seems to be the driver of the changes we see in Alzheimer's pathology, but we also know the microbiome is changing," says University of Chicago neurobiologist Sangram Sisodia. "So, there's this crosstalk between the two."

In a second study conducted by several of the same researchers, an Alzheimer's drug candidate called sodium oligomannate (or GV-971) was tested on mice. It only had an effect on reducing amyloid beta deposits and altering the gut microbiome of the male animals, implying something in female mice – perhaps linked to the gut microbiome and to estrogen – affects biological markers associated with Alzheimer's disease.

Alzheimer's is an incredibly complex disease, making it very tough to study: we're not sure, for example, if amyloid beta clumps are a cause or a consequence of Alzheimer's. Research like this can help in unpicking some of the finer details.

"We see in the current study that estrogen levels always have an impact on amyloid deposition," says Sisodia. "If you take away the source of estrogen in mice at a very early stage, amyloid deposition goes away. It's pretty remarkable."

With more research, findings from studies like these might help us to treat Alzheimer's more effectively or to rethink existing practices – it's worth noting that hormone replacement therapy is often used to maintain estrogen levels in postmenopausal women.

Of course, stopping estrogen production isn't a healthy option either, which is why the researchers want to look in more detail at the chemical reactions that might be taking place, potentially revealing more about how Alzheimer's disease and the gut are somehow connected.

"How do those pathways interact? And how does that lead to the changes in brain function?" says Sisodia "That's all yet to be determined."

The two studies have been published in Scientific Reports and Molecular Neurodegeneration.