30 October 2025

Sex-based differences in biomarkers for Alzheimer’s Disease (AD) can be observed in the cerebrospinal fluid (CSF) years before the disease manifests. The Women’s Brain Foundation (WBF) in collaboration with an international team of scientists led by researchers from the Barcelonaβeta Brain Research Centre (BBRC) in Spain, is proud to share a new publication uncovering important sex differences in AD biomarkers in individuals who do not yet experience cognitive symptoms. 

Funded by Roche Diagnostics, the study analysed over 900 cognitively unimpaired participants, including participants in the ALFA+ cohort, part of the ALFA study (ALzheimer’s and FAmilies) at the BBRC, supported by the ”la Caixa” Foundation, which follows 400 cognitively unimpaired participants at risk for Alzheimer’s disease, and participants in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center (WRAP/WADRC; N=548) at Wisconsin University. Multiple CSF biomarkers linked to Alzheimer’s pathology, neurodegeneration, synaptic function, glial reactivity, and vascular health were measured. 

Key Findings

Sex differences in biomarker levels: 

• Women had higher levels of synaptic biomarkers 
• Men had higher levels of biomarkers linked to neurodegeneration, glial activation, and vascular dysregulation  

Diagnostic accuracy: 

• Despite these differences, core Alzheimer’s biomarkers (such as Aβ42/40 and phosphorylated tau/Aβ42 ratios) were equally accurate in women and men for identifying amyloid positivity.  
• Sex modifies associations with amyloid burden: The link between CSF biomarkers and amyloid accumulation in the brain was stronger in women, suggesting that these biomarkers are more indicative of Aβ accumulation in the brain of women. 

“We found that the levels of some CSF biomarkers differ between men and women, but both sexes can be classified equally well when it comes to detecting amyloid in the brain, supporting their use in clinical trials without the need for sex-specific cutoffs. However, their associations with amyloid burden can vary by sex, which may have implications for their prognosis or monitoring applications.”, explains Dr. Marta Milà, first author of the study, postdoctoral researcher at Northern California Institute for Research and Education (NCIRE) and associated researcher at the BBRC.  

Dr. Antonella Santuccione Chadha, CEO and Founder of the Women’s Brain Foundation, added: “Understanding sex differences in biomarker patterns brings us closer to precision medicine in Alzheimer’s, where prevention and treatment strategies can be tailored for men and women.” 

This study highlights the importance of integrating sex as a biological variable in Alzheimer’s research and paves the way for more personalized approaches to brain health. 

About the Women’s Brain Foundation 

The Women’s Brain Foundation is an independent Swiss-based non-profit research institute committed to closing the gender gap in brain and mental health. Through sex- and gender-precision research, advocacy, and education we champion equity in neuroscience and care. We foster a global community of interdisciplinary experts who conduct research and education, provide scientific advice and support, adapt emerging technologies such as AI to create solutions for better brain and mental health. Together, we strive to unlock the full potential of the women’s brain capital and drive meaningful change worldwide.

Learn about the recently launched WBF Educational Academy: https://www.womensbrainproject.com/membership/ 

Website: www.womensbrainproject.com 

Media Contact: 
Email: info@womensbrainfoundation.org