Unlocking the Link: How Menopause and Synapse Health May Elevate Alzheimer’s Risk

New research suggests that the age at which women go through menopause could influence their risk of developing Alzheimer’s disease through effects on synapse health. The study found that women who experience menopause at a younger age tend to show stronger links between poor synapse health and higher levels of proteins related to Alzheimer’s, as well as sharper declines in cognitive function. Interestingly, these associations were less evident in women who underwent hormone replacement therapy.

Madeline Wood Alexander, a graduate student at the University of Toronto, emphasized the importance of both hormonal changes and synapse health in impacting Alzheimer’s risk for women. This insight comes from the study titled “The interplay between age at menopause and synaptic integrity on Alzheimer’s disease risk in women,” published in Science Advances.

Alzheimer’s disease gradually impairs memory and cognitive abilities, eventually leading to dementia, where daily life is significantly affected. The brains of those with Alzheimer’s show the damaging buildup of proteins like beta-amyloid and tau, which harm nerve cells. Synapses—the connections between these nerve cells—begin to deteriorate early on, closely linked to cognitive decline.

Women face a higher risk of Alzheimer’s than men, with around two-thirds of dementia patients being female. They also tend to experience faster cognitive declines, even when having similar levels of toxic proteins in their brains as men. While the exact reasons for this discrepancy are still being researched, menopause and its hormonal effects may play a vital role.

As women enter menopause, there is a drop in estrogen levels, which have neuroprotective properties. Early menopause, associated with lower estrogen exposure over time, has been linked to a higher risk of dementia and increased tau protein build-up in the brain. Estrogen plays a key role in forming and maintaining synapses. Studies in animals have shown that declines in estradiol, the strongest form of estrogen, negatively affect synapse health.

Despite knowing the role of hormones in brain health, there is still a lack of research exploring how these hormonal changes interact with synapse function and contribute to Alzheimer’s disease. The recent study looked at data from 268 women who participated in the Rush Memory and Aging Project, focusing on those who experienced spontaneous menopause around age 50.

The findings revealed that lower levels of certain proteins related to synapses were connected to higher beta-amyloid buildup, but not directly to tau or cognitive function. However, the age at which menopause occurred did affect the relationship between synaptic health and other outcomes. Specifically, younger age at menopause strengthened the ties between poor synapse health and greater tau burden, as well as faster cognitive declines.

Interestingly, this pattern was less pronounced in women who had received hormone therapy, which can help manage menopause symptoms by providing additional hormones like estrogen.

These insights suggest that both synapse health and hormonal factors might together shape Alzheimer’s risk in women. “Addressing both these factors could boost resilience against dementia,” the researchers noted. Yet, the exact mechanisms at play remain unclear.

There is a pressing need for further research focused on women’s health, which has often been overlooked. Jennifer Rabin, one of the senior authors of the study, stressed that prioritizing such research will not only fill critical gaps in knowledge but also lead to finding ways to keep all brains healthy longer.

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