Scientists have suggested that lipids could play a role in Alzheimer’s, their study indicating a possible causal link between the disease and fatty acids, and showing that women with the condition have fewer omega fatty acids in their blood than healthy women. But a clinical trial is necessary to confirm the link, they added.
They said their analysis of lipids – fat molecules that perform many essential functions in the body – in the blood found a noticeable loss of unsaturated fats, like those containing omega fatty acids, in the blood of women with Alzheimer’s disease compared with healthy women.
They found no significant difference in the same lipid molecule composition in men with Alzheimer’s disease compared to healthy men, which suggests that those lipids have a different role in the disease according to sex. Fats perform important roles in maintaining a healthy brain, so this study could indicate why more women are diagnosed with the disease.
The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association by scientists from King’s College London and Queen Mary University London, is the first to reveal the important role lipids could have in the risk for Alzheimer’s between the sexes.
“Women are disproportionately impacted by Alzheimer’s and are more often diagnosed with the disease than men after the age of 80. 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 – opening new avenues for research,” said senior author Dr Cristina Legido-Quigley, Reader in Systems Medicine, King’s College.
The scientists took plasma samples from 841 participants who had Alzheimer’s Disease and mild cognitive impairment, and cognitively health controls, and measured for brain inflammation and damage.
They used mass spectrometry to analyse the 700 individual lipids in the blood. Lipids are a group of many molecules. Saturated lipids are generally considered as “unhealthy’” or “bad” lipids, while unsaturated lipid, which sometime contains omega fatty acids, are generally considered “healthy”.
The team saw a steep increase in lipids with saturation in women with Alzheimer’s compared with the healthy group. The lipids with attached omega fatty acids were the most decreased in the Alzheimer’s group.
Legido-Quigley added: “Our study suggests that women should make sure they are getting omega fatty acids in their diet – through fatty fish or via supplements. However, we need clinical trials to determine if shifting the lipid composition can influence the biological trajectory of Alzheimer’s.”
Dr Asger Wretlind, first author of the study from the School of Cancer & Pharmaceutical Sciences, also King’s College, said: “Scientists have known for some time that more women than men are diagnosed with Alzheimer’s disease.
“Although this still warrants further research, we were able to detect biological differences in lipids between the sexes in a large cohort, and show the importance of lipids containing omegas in the blood, which has not been done before. The results are very striking and now we are looking at how early in life this change occurs in women.”
Dr Julia Dudley, Head of Research at Alzheimer’s Research UK, said: “In Britain, two in three people with dementia are women. This could be linked to living longer, or other risk factors like social isolation, education, or hormonal changes from menopause.
“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.”
Study details
Lipid profiling reveals unsaturated lipid reduction in women with Alzheimer's disease
Asger Wretlind, Jin Xu, Wenqiang Chen, Latha Velayudhan, Nicholas J. Ashton, Henrik Zetterberg, Petroula Proitsi, Cristina Legido-Quigley.
Published in Alzheimer's & Dementia on 20 August 2025
Abstract
Introduction
Alzheimer's disease (AD) is a devastating neurological disease that disproportionately affects women. This study aimed to investigate sex-specific single lipids associated with AD.
Methods
Plasma samples from 841 participants, comprising 306 individuals with AD, 165 with mild cognitive impairment (MCI), and 370 cognitively healthy controls were curated from the AddNeuroMed cohort. Lipidomics identified 268 single lipids for each sample. We investigated sex-specific associations from lipid modules and single lipids to AD and probed for causality with mediation analyses.
Results
Three modules associated with AD in the female subset and one in the male subset (P < 0.05). In the female participants with AD, lipid families containing highly unsaturated fatty acids were reduced and those containing saturated lipids were increased (q value < 0.05). The effects of unsaturated phospholipids on AD were not mediated via cholesterol, low-density lipoprotein, or apolipoprotein B.
Discussion
Women with AD have lower unsaturated plasma lipid levels compared to controls.
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