Circulating Homocysteine and Choroid Plexus Volume Across the Alzheimer’s Disease Continuum: Cross-Sectional and Progression-Related Associations
Simple Summary Alzheimer’s disease progression involves complex changes in both the brain and the body, but the biological links between peripheral metabolic alterations and brain structural changes remain unclear. This study examined whether elevated blood homocysteine levels were associated with larger choroid plexus volume, an MRI-derived measure of the choroid plexus, a structure involved in maintaining the brain environment. In a large cohort covering normal cognition, mild cognitive impairment, and Alzheimer’s disease dementia, higher blood homocysteine levels were associated with increased choroid plexus volume, and larger choroid plexus volume was associated with a higher risk of progression from mild cognitive impairment to Alzheimer’s disease dementia. Exploratory reanalysis of independent postmortem single-nucleus and spatial transcriptomic datasets identified choroid plexus epithelial expression states involving one-carbon metabolism-related genes and spatial organization near vascular compartments. These independent transcriptomic findings provide tissue-level biological context for the associations observed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and support further validation of these epithelial expression states.