Blood-brain barrier alterations are associated with the development of brain bleeds in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a disease of the small blood vessels of the brain. A possible consequence of this disease is rupture of the blood vessels, leading to brain bleeds. Almost a quarter of the elderly population (>55 years) has moderate-to-severe CAA, yet, our understanding of this vascular pathology and how it can lead to these devastating clinical consequences is limited.

Researcher Lieke Jäkel, working in the research group of Marcel Verbeek from the department of Neurology, hypothesized whether alterations of the blood-brain barrier (BBB) could be associated with the development of brain bleeds as a consequence of CAA. The BBB plays an important role in protecting the brain from harmful substances in the blood, and decreased BBB integrity and functioning may be associated with impaired vascular integrity. Their results were published in Brain Pathology on May 19^th 2024. The researchers investigated the levels of BBB protein claudin-5 in two different brain regions (occipital and temporal lobe tissue) using immunohistochemistry. They studied brain tissue of over 100 patients, including CAA patients with brain bleeds, CAA patients without brain bleeds, and control cases.

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The research group demonstrated that in both brain regions, CAA patients with brain bleeds had decreased levels of claudin-5 compared to CAA patients without brain bleeds. The changes of protein levels were not only observed in patients who had suffered a recent brain bleed, but also in patients who had a brain bleed several years before death. The researchers concluded that the changes in protein levels are not an acute response to the brain bleed, but may rather provide a mechanistic explanation for the occurrence of brain bleeds as a consequence of CAA.

The research group is building on the current findings by studying other vascular proteins, to further decipher how CAA leads to brain bleeds.

Read the study here: Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage - PubMed (nih.gov)

Jäkel, L., Claassen, K., De Kort, A. M., Jolink, W. M. T., Vermeiren, Y., Schreuder, F., Küsters, B., Klijn, C. J. M., Kuiperij, H. B., & Verbeek, M. M. (2024). Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage. Brain Pathol, e13270. https://doi.org/10.1111/bpa.13270