Evaluating Basigin as a Potential Biomarker of Blood-Brain Barrier Dysfunction in Cerebral Amyloid Angiopathy

Blood-brain barrier (BBB) dysfunction may be involved in the pathophysiology of neurodegenerative disorders, including sporadic cerebral amyloid angiopathy (CAA). Because basigin (BSG) may induce activity of matrix metalloproteinases and thereby BBB breakdown, we investigated BSG expression in CAA brain tissue with immunohistochemistry and as cerebrospinal fluid biomarker for BBB dysfunction in patients with CAA.

Using immunohistochemistry, we quantified BSG expression within the cortical microvasculature of the temporal lobe of 50 CAA patients (16 with intracerebral haemorrhage [CAA-ICH] and 34 without intracerebral haemorrhage [CAA-NH]) and 35 controls. To investigate whether BSG is expressed at another brain barrier, choroid plexus tissue was qualitatively assessed. Additionally, we compared cerebrospinal fluid levels of BSG between 40 CAA patients and 27 healthy controls using ELISA.

Cortical vessels, in particular capillaries, were positive for BSG. Median %area of BSG expression was increased in CAA cases (1.02%, IQR [0.63-1.68]) compared with controls (0.65%, IQR [0.43-1.01], p = 0.013). Moreover, we observed more BSG staining in CAA-NH (1.23%, IQR [0.90-2.0]) than in CAA-ICH (0.58%, IQR [0.24-1.00], p = 0.001) and controls (p < 0.001). Choroid plexus epithelial cells showed apical BSG expression, whereas endothelial cells were negative. The median BSG concentration in CSF was decreased in CAA (11.0 ng/mL, IQR [10.1-13.8]) compared with controls (13.00 ng/mL, IQR [11.5-14.5], p = 0.02).

CSF concentrations of BSG may be related to altered expression at the BBB; the BSG concentrations in CSF may thus serve as a biomarker of BBB function, although a contribution of choroid plexus epithelial BSG cannot be entirely excluded. Independent cohorts are needed to replicate these observations before we can conclude that reduced CSF concentrations of BSG may indicate an alteration of the BBB in patients with CAA.