Brain MRI signatures across sex and CSF Alzheimer’s disease biomarkers
Published in Brain Communications, 2025
Recommended citation: Cheng, Y., He, Y., Gopinath, K., Billot, B., Iglesias, J. E., Wu, C.-Y., Dodge, H., Wills, A.-M., Carlyle, B., Kivisäkk, P., Hyman, B. T., Arnold, S. E., & Das, S. (2025). Brain MRI signatures across sex and CSF Alzheimer's disease biomarkers. Brain Communications, 7(3), fcaf210. https://doi.org/10.1093/braincomms/fcaf210
We examined how cerebrospinal fluid (CSF) amyloid and tau biomarkers relate to sex-specific brain structural changes using MRI. The study included 306 patients (mean age 68.4 years, 43% female) from Massachusetts General Hospital, with validation across three additional datasets totaling 3,137 participants. Patients were categorized by CSF biomarker status (amyloid and tau positive/negative). Key findings showed that control groups displayed more distinct and robustly correlated structural clusters compared to biomarker-positive groups. Amyloid positivity was associated with subcortical, cerebellar, and brainstem atrophy, particularly in the thalamus and amygdala. Tau positivity in the presence of amyloid demonstrated general brain shrinkage through enlargement of extracerebral CSF. Notably, A+T+ individuals showed lower sex differences in connectivity patterns compared to other biomarker groups. These results reveal distinct neurodegeneration patterns across biomarker categories and identify sex-specific variations in brain volume changes, potentially informing personalized diagnostic approaches in Alzheimer’s disease assessment.