A leaky gut contributes to postural dysfunction in patients with Alzheimer's disease.

Background: Postural dysfunction is a common problem in patients with Alzheimer's disease (AD) and may lead to functional dependency and increasing morbidity and mortality. However, the pathophysiology of postural dysfunction in AD patients remains poorly understood. Objectives: Elevated intestinal permeability is an underlying contributor to multiple diseases, including AD. We aimed to investigate the association of elevated intestinal permeability with postural dysfunction in AD patients. Design Setting Participants Measurements: We conducted a cross-sectional, observational study on older adults, including controls and AD patients. We investigated the associations of postural balance with plasma zonulin, a marker of elevated intestinal permeability in geriatric controls (n = 74) and patients with mild (n = 71) and moderate (n = 66) AD. We used a standardized physical performance battery to measure balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), and gait speed as markers of physical capacity. Results: AD patients exhibited lower balance scores, HGS, and gait speed and higher plasma zonulin than in controls (all p < 0.05). Plasma zonulin levels demonstrated significant areas under the curves in diagnosing poor balance in AD patients (all p < 0.05). Moderate AD was associated with lower balance and physical capacity, and higher zonulin than mild AD (ALL P < 0.05). Poor scores on balance scale were associated with higher expressions of markers of inflammation, oxidative stress, and muscle damage providing a mechanistic link between increased intestinal permeability and postural dysfunction in AD patients. Conclusion: The results of our study show that plasma zonulin measurement may be used to diagnose postural dysfunction in AD patients. The study is relevant to non-ambulant and/or comatose AD patients with postural dysfunction. Our findings also highlight the therapeutic potential of repairing the intestinal leak to improve postural control and reduce the risk of falls in AD patients.