Zonulin and blood–brain barrier permeability are dissociated in humans

Zonulin and blood-brain barrier permeability are dissociated in humansDear Editor, Zonulin, or prehaptoglobin-2, mediates intestinal permeability in coeliac disease through the regulation of epithelial tight junctions.1 Tight junction breakdown at the blood-brain barrier (BBB) is a common pathological finding in neurological disease, 2 and several in vitro and preclinical in vivo studies have suggested that zonulin plays a role in modulation of BBB permeability, 3-6 yet using multiple methods, we here consistently find that zonulin plays a negligible role in human BBB permeability.Zonulin is a member of the MASP (mannose-binding lectin-associated serine protease) family of proteins, and elevated serum zonulin levels have been reported in a number of neurological conditions such as multiple sclerosis 7 and Alzheimer's disease.8 The significance of zonulin upregulation in these neurological diseases is not certain.Specifically, it is not clear whether zonulin is an epiphenomenon, or has an effect on the brain, whether directly or mediated through the gut-brain axis.To study the association between zonulin and BBB permeability in healthy individuals and patients with neurological disease, we employed two techniques to measure permeability across a range of molecular weights: Q Alb , or the quotient of cerebrospinal fluid to serum albumin (60 000 Da) in Study A and dynamic contrastenhanced magnetic resonance imaging with gadobutrol tracer (600 Da) in Study B (Supplemental Methods).Participant characteristics are shown in Table 1.Out of a total of 217 cases (including people with neurological conditions and control individuals) across both studies, 58 (27%) individuals tested negative for serum zonulin using a novel enzyme-linked immunosorbent assay (ELISA) (Supplemental Methods).Serum zonulin concentration followed a non-Gaussian distribution with a range of 0-11 µg/ml.There were no effects of sex, age or disease status (disease vs. control) on zonulin concentrations (analysis of covariance, F(3,216) = 1.06, p = .37).In order to assess zonulin using a complementary dual approach,

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   The blood–brain barrier in systemic infection and inflammation · 2021

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