Disease Area Neurological, Imaging

Breakdown Breakthrough

For researchers who seek to better understand neurological disorders, vascular dysfunction is emerging as a leading area of interest, with several studies beginning to unpick its contribution to cognitive impairment. Small vessel disease (SVD), characterized by the failure of blood vessels in the brain to fully dilate, is well associated with neurological disorders: it effects 50 percent of dementia sufferers worldwide, including those who have Alzheimer's disease (AD).

For a long time, the assumption was that SVD was a direct consequence of the vasculotoxic effects of accumulating amyloid-beta (aβ) and tau – but a new study reported in Nature Medicine suggests there’s much more to the story (1). In an attempt to test the long-held assumption, Berislav Zlokovic and his team at the University of California, USA, turned to a combination of dynamic contrast-enhanced magnetic resonance (DCE-MRI) technology and a novel cerebrospinal fluid biomarker for blood brain barrier (BBB) permeability. “To our surprise, we found that BBB breakdown is an early biomarker of cognitive dysfunction that is independent of Alzheimer’s diseases classical biomarkers - aβ and tau,” says Zlokovic. More specifically, individuals with early cognitive dysfunction were developing brain capillary damage and BBB breakdown in the hippocampus.

Zlokovic notes that future longitudinal studies will be required to confirm the early results, but he believes theres is translational potential in his BBB biomarker. “A similar test is routinely used for clinical diagnosis and evaluation of treatments in patients with multiple sclerosis, brain tumourstumors, brain metastasis, infections – a whole range of neurological pathologies,” he says. “It needs to be adapted for disorders associated with cognitive dysfunction to detect more moderate regional BBB breakdowns in areas, such as the hippocampus, which is the first to be affected.”

Next, the team plan to work on ways to understand the role of BBB breakdown in cognitive dysfunction in people carrying genetic risk factors for Alzheimer's disease - such as apoE4 and presinilin 1 mutations.

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  1. D A Nation et al., “Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction.” Nat Med [Epub ahead of print] (2019). PMID: 30643288.
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Jonathan James

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