Plasma lipidomics in women with Alzheimer’s disease: Exploring associations with ApoE genotype and cardiovascular risk

Autores de IIS La Fe

• Laura Ferré González

  Autor

• María Del Carmen Peña Bautista

  Autor

• Lourdes Álvarez Sánchez

  Autor

• Mar Pereto Pamblanco

  Autor

• Lorena García Vallés

  Autor

• Luis Raga Rodríguez

  Autor

• Marta Isabel Roca Marugán

  Autor

• 

  Miguel Baquero Toledo

  Autor

• 

  María Consuelo Cháfer Pericás

  Autor

Grupos

• Grupo de Investigación en Enfermedad de Alzheimer (GINEA)

Abstract

BACKGROUND Alzheimer’s disease (AD) is the leading cause of dementia, with an increasing incidence due to population aging. Approximately two-thirds of the people affected are women, possibly due to biological and hormonal factors. Also, lipids could play an important role in AD and show associations with cognitive impairment. apolipoprotein E allele 4 (ApoE e4) genotype and cardiovascular (CV) risk lipid ratios could be relevant in lipidomic studies. OBJECTIVE This work aims to identify specific alterations in plasma lipid profiles associated with AD in women and to explore these alterations related to Apolipoprotein E (ApoE) and 2 CV risk lipid ratios. METHODS A lipidomic mass spectrometry–based method was applied to plasma samples from a clinical cohort of women. The patients were accurately classified into AD (n = 76) and non-AD (n = 74) groups by cerebrospinal fluid amyloid beta (Aß)42/Aß40 levels. The identified lipid species were evaluated and grouped into families and subfamilies. The lipids with significant differences between groups were examined in relation to ApoE genotype and 2 CV risk ratios (total cholesterol/high-density lipoprotein [HDL], triglycerides/HDL). RESULTS Fatty acyls and monoacylglycerols showed higher levels in AD compared with non-AD, while diacylglycerols (DAGs) showed lower levels in AD. Also, specific subfamilies correlated with aging, CV risk, AD biomarkers, and cognitive status. Of the 627 lipid species detected, 45 showed statistically significant differences between groups, and some of them [lysophosphatidylcholine (24:1), diacylglycerol (18:0/18:1), and triacylglycerol (50:3)] showed significant associations with ApoE genotype and CV risk. CONCLUSION This study identified associations between lipid profiles in women and AD pathology, ApoE e4 genotype, and high CV risk ratios. © 2026 National Lipid Association.

Keywords

• Alzheimer; Biomarker; Cholesterol; Lipids; Plasma; Women