Serum zonulin levels are increased in Alzheimer's disease but not in vascular dementia

Background: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly. Aim: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI). Methods: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls. Results: Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders. Discussion: We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones. Conclusions: Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration.