Contribution of blood-brain barrier-related blood-borne factors for Alzheimer’s disease vs. vascular dementia diagnosis: A pilot study

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of neurodegenerative dementia among the elderly with similar symptoms of cognitive decline and overlapping neuropsychological profiles. Biological markers to distinguish patients with VaD from AD would be very useful. We aimed to investigate the expression of blood-brain barrier (BBB)-related blood-borne factors of soluble low-density lipoprotein receptor-related protein 1 (sLRP1), cyclophilin A (CyPA), and matrix metalloproteinase 9 (MMP9) and its correlation with cognitive function between patients with AD and VaD.Plasma levels of sLRP1, CyPA, and MMP9 were analyzed in 26 patients with AD, 27 patients with VaD, and 27 normal controls (NCs). Spearman's rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and imaging references. Receiver operating characteristic (ROC) curve analysis was used to discriminate the diagnosis of AD and VaD.Among these BBB-related factors, plasma CyPA levels in the VaD group were significantly higher than that in the AD group (p < 0.05). Plasma sLRP1 levels presented an increasing trend in VaD while maintaining slightly low levels in patients with AD (p > 0.05). Plasma MMP9 in different diagnostic groups displayed the following trend: VaD group > AD group > NC group, but the difference was not statistically significant (p > 0.05). Furthermore, plasma sLRP1 levels were positively related to MoCA scores, and plasma CyPA levels were significantly correlated with MTA scores (p < 0.05) in the AD group. Plasma MMP9 levels were negatively correlated with MoCA scores (p < 0.05) in the VaD groups. No significant correlation was detected between the other factors and different cognitive scores (p > 0.05). ROC analysis showed a good preference of plasma CyPA [AUC = 0.725, 95% CI (0.586-0.865); p = 0.0064] in diagnosis.The plasma CyPA level is a reference index when distinguishing between an AD and subcortical ischemic vascular dementia (SIVD) diagnosis. Blood-derived factors associated with the BBB may provide new insights into the differential diagnosis of neurodegenerative dementia and warrant further investigation.