Interactions between hormones and the gut microbiota may be the cause of the higher incidence of Alzheimer’s disease in women
In the United States, about two out of three Alzheimer’s patients are women. In Spain, according to the Spanish Society of Neurology, women over 80 years old are almost three times more likely to suffer from this disease than men of the same age.
Attempts have been made to explain this statistic in part by the fact that women tend to live longer than men. However, researchers suspect there could be more. Now two new studies raise the possibility that complex interactions between hormones and changes in the gut microbiota may be contributing factors.
In a study conducted by researchers at the University of Chicago, experiments in mice found that the female hormone estrogen was significantly linked to the formation of clumps of amyloid beta protein in the brain, a key feature of Alzheimer’s disease.
When the gut microbiota of female mice bred to develop Alzheimer’s-like disease was altered by antibiotics, their blood estrogen levels skyrocketed.
Neurofibrillary tangles in the hippocampus of an elderly person with Alzheimer’s-related pathology. Patho
Additionally, when estrogen production was prevented in the mice, fewer amyloid deposits were observed in their brain tissues. Changes in the composition of gut bacteria were also observed when these mice without ovaries were given estrogen supplementation to restore hormone levels.
Given the team’s previous work showing that antibiotics had an effect on reducing amyloid beta deposits only in male mice, it appears that estrogen plays an important role in the mechanisms underlying the pathology. Most likely in combination with the gut microbiome, the mix of microorganisms in the stomach and associated ducts.
“Estrogen appears to be the driver of the changes we see in Alzheimer’s pathology, but we also know that the microbiome is changing,” says Sangram Sisodia, a neurobiologist at the University of Chicago. “So there’s this crosstalk between the two.”
In a second study by several of the same researchers, an Alzheimer’s drug candidate called sodium oligomannate (or GV-971) was tested in mice. It only had an effect on reducing amyloid-beta deposits and altering the gut microbiome of male animals, suggesting that something in the female mice – possibly related to the gut microbiome and estrogen – was changing the biology associated with Alzheimer’s disease Marker influenced.
Alzheimer’s is an incredibly complex disease, which is why it is very difficult to study: for example, we are not sure whether amyloid beta clumps are a cause or a consequence of Alzheimer’s. Research like this can help unravel some of the finer details.
“In the current study, we see that estrogen levels always have an influence on amyloid deposition,” says Sisodia. “When the estrogen source is removed at a very early stage in mice, amyloid deposition disappears.” “It’s quite surprising.”
With more research, insights from studies like this could help us treat Alzheimer’s more effectively or 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 researchers want to take a closer look at the chemical reactions that may be occurring and perhaps learn more about the connection between Alzheimer’s and the gut.
«How do these pathways interact? And how do they lead to changes in brain function?” says Sisodia. “All of this still needs to be sorted out.”
REFERENCE
Early modulation of the gut microbiome by female sex hormones alters amyloid pathology and microglial function
Sodium oligomannate alters gut microbiota, reduces cerebral amyloidosis and reactive microglia in a sex-specific manner
