Cross-sectional investigation of choroid plexus calcification, cardiovascular risk score, and APOEε4 Status in cognitively normal cohort

The choroid plexus (CP), known for producing cerebrospinal fluid, is increasingly implicated in the pathogenesis of Alzheimer’s disease (AD). Neuroimaging studies document structural CP alterations in aging and AD. One such alteration, calcium deposition, increases with age and is typically considered benign, though the mechanism and clinical significance of CP calcification remain uncertain. Given established association between peripheral vascular calcification and cardiovascular risk, we hypothesized that the volume of calcium within CP would correlate with systemic cardiovascular health. Based on prior findings of APOEε4-specific associations between CP calcium and neurodegeneration, participants were stratified by APOEε4 status, a strong genetic risk factor for AD also implicated in cardiovascular disease. In this retrospective analysis of 105 adults (mean age 58.9 years; 39 APOEε4+), we examined whether CP calcium correlates with cardiovascular risk in cognitively normal adults. CP calcium was quantified using a previously validated MRI–CT method. Spearman correlations assessed the association of CP calcium and Framingham Cardiovascular Risk Score (FCRS), as well as individual cardiovascular risk factors. Overall, CP calcium was not associated with FCRS. Among APOEε4− subjects, CP calcium correlated positively with FCRS (ρ = 0.26, p = 0.03). Conversely, APOEε4+ subjects showed an unexpected inverse correlation between CP calcium and systolic blood pressure (ρ = −0.38, p = 0.02). Greater CP calcium in association with higher FCRS in APOEε4− individuals mirrors the established link between CAC and cardiovascular risk, suggesting potential for CP calcium as an intracranial marker of vascular health. Divergent findings in APOEε4+ carriers may reflect CP-specific pathways relevant to APOEε4-driven AD pathogenesis.