While researchers determined years ago that Alzheimer’s disease disproportionately affects women, they’ve spent just as much time debating the disparity.
Now new research hints that maybe biology plays an outsized role. Women with Alzheimer’s appear to have dramatic deficits in specific blood lipids pivotal to brain health.
“Women are disproportionately impacted by Alzheimer’s … and are more often diagnosed with the disease than men after the age of 80,” corresponding author Cristina Legido-Quigley, PhD, explained. “One of the most surprising things we saw when looking at the different sexes was that there was no difference in these lipids in healthy and cognitively impaired men, but for women this picture was completely different. The study reveals that Alzheimer’s lipid biology is different between the sexes, opening new avenues for research.”
The research, led by King’s College London (in collaboration with international partners), analyzed blood plasma from 841 older adults enrolled in the AddNeuroMed study. Participants included 306 diagnosed with Alzheimer’s disease, 165 with mild cognitive impairment (MCI), and 370 cognitively healthy controls.
Using a technique called lipidomics, the scientists profiled 268 lipids. The team then compared lipid patterns by sex to see how they related (if at all) to cognitive decline.
What the researchers found was clear. Women, not men, drove the strongest lipid changes linked to Alzheimer’s.
Unsaturated Lipids in Short Supply
Women with Alzheimer’s showed much lower levels of highly unsaturated lipids, including triglycerides, phosphatidylcholines (PCs), and phosphatidylethanolamines (PEs). These molecules usually carry omega-3 fatty acids, such as DHA and EPA, which studies have shown support memory, synaptic function, and overall brain resilience.
At the same time, women with Alzheimer’s showed increases in more saturated and monounsaturated lipids. The takeaway suggested a shift away from lipids that promote flexibility in cell membranes toward those that might harden them, potentially impairing brain signaling and plasticity.
Male Alzheimer’s patients, on the other hand, showed no noteworthy lipid changes compared to their healthy peers.
Cognitive and Biological Links
The lipid differences weren’t just biochemical flukes. They mirrored cognition. Women with lower unsaturated lipid levels performed worse on the Mini-Mental State Exam.
Several of the depleted lipids also corresponded to higher levels of biomarkers for brain injury and inflammation.
Notably, cholesterol, LDL, and apolipoprotein B didn’t mediate the effects of these unsaturated lipids, which hints that lipid shifts in women with Alzheimer’s reflect a separate biological pathway.
A Role for Diet and Hormones?
The paper adds to mounting evidence that women’s metabolism, especially around fatty acids, differs ever more than expected from men’s. Women tend to have higher levels of omega-3 fatty acids in their tissues, but that advantage might fade with Alzheimer’s.
The study raises questions about whether dietary interventions – such as omega-3 supplementation – could help mitigate the decline in unsaturated lipids and slow disease progression in women.
“Our study suggests that women should make sure they are getting omega fatty acids in their diet – through fatty fish or via supplements,” Legido-Quigley added. “However, we need clinical trials to determine if shifting the lipid composition can influence the biological trajectory of Alzheimer’s Disease.”
It also dovetails with research showing hormone replacement therapy might improve cognition in women carrying the APOE ε4 genetic risk variant. Whether these benefits relate to lipid metabolism remains to be tested.
Research and Treatment Implications
The study’s lead authors emphasize that sex-stratified analysis is essential in Alzheimer’s research. Pooling men and women together, they argue, risks masking meaningful biological differences.
The results could also influence future drug development. For example, cholesterol and LDL levels partially mediated highly unsaturated lipids, supporting the idea that statins might have sex-specific benefits in staving off cognitive decline.
“While this study shows that women with Alzheimer’s had lower levels of some unsaturated fats compared with men, further work is needed. This includes understanding the mechanisms behind this difference and finding out if lifestyle changes, including diet, could have a role. Future research should also be carried out in a more ethnically diverse population to see if the same effect is seen,” Julia Dudley, PhD, head of Research at Alzheimer’s Research UK said in a statement. “Understanding how the disease works differently in women could help doctors tailor future treatments and health advice. Alzheimer’s Research UK is proud to be funding this work that will bring us a step closer to a cure.”
The research adds to a growing body of evidence that women’s heightened Alzheimer’s risk can’t be explained by longevity alone. Instead, molecular differences could be the difference.
A Shift Toward Precision Medicine
If validated, these findings could open the door to more custom approaches to Alzheimer’s prevention and care. Biomarkers that track lipid changes could help identify women at higher risk. And it could do so much sooner. Interventions, whether nutritional, hormonal, or pharmacological, could possibly be tailored to address those deficits.
As Alzheimer’s rates creep up worldwide, a growing numbers of researchers insist that precision medicine approaches that account for sex differences will be vital. For now, the message is clear. In the biology of Alzheimer’s, what’s true for men isn’t necessarily true for women.
Further Reading
Benefits and Risks of New Tests for Alzheimer’s Disease
