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

## TL;DR

This study explores basigin (BSG) as a potential biomarker for blood-brain barrier dysfunction in cerebral amyloid angiopathy (CAA), finding altered BSG levels in patients compared to controls.

## Contribution

The study introduces BSG as a novel candidate biomarker for blood-brain barrier dysfunction in CAA, supported by immunohistochemical and cerebrospinal fluid analyses.

## Key findings

- Cortical BSG staining is increased in CAA cases without intracerebral hemorrhage compared to controls.
- Cerebrospinal fluid BSG concentrations are decreased in CAA patients compared to healthy controls.
- Choroid plexus epithelial cells also express BSG, which may affect the specificity of BSG as a BBB biomarker.

## Abstract

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.

Cerebrovascular BSG staining is increased in CAA‐NH cases compared to CAA‐ICH and control.The CSF BSG concentration is decreased in patients with CAA compared to control.Altered cerebrovascular BSG regulation may contribute to BBB‐dysfunction in CAA.

Cerebrovascular BSG staining is increased in CAA‐NH cases compared to CAA‐ICH and control.

The CSF BSG concentration is decreased in patients with CAA compared to control.

Altered cerebrovascular BSG regulation may contribute to BBB‐dysfunction in CAA.

Basigin (BSG) is a potential biomarker for blood‐brainbarrier dysfunction since link via matrix metalloproteinases. In a clinical cohort and in post‐mortem cortical tissue, we compared the CSF levels and vascular BSG immunoreactivity between patients with Cerebral amyloid angiopathy (CAA) and control cases. The CSF BSG concentration is decreased in patients with CAA compared to control while vascular BSG is increased in CAA cases. Because the choroid plexus also expresses BSG the specificity of this BBB‐biomarker is reduced.