Dietary elimination of gluten attenuates amyloid-β and tau pathology in Alzheimer’s disease-like in aluminum chloride-induced rats: an experimental animal study

Abstract This study evaluates the comparative neuroprotective efficacy of a multi-component dietary pattern (the Mediterranean-DASH Intervention for Neurodegenerative Delay) versus a single-component elimination strategy (gluten-free diet) in an AlCl₃-induced rat model of Alzheimer’s disease. Sprague–Dawley rats were randomly divided into six groups (n = 6 each) and fed a balanced diet, the MIND diet, or a gluten-free diet, with or without AlCl₃ (100 mg/kg/day) administered orally for 8 weeks. AlCl₃ administration significantly elevated Aβ, total tau, and p-Tau S231 compared to non-induced controls ( P < 0.001 for all AD effects). Conversely, all three diets differed significantly from one another for total tau and p-Tau S231 ( P < 0.05 for all comparisons). Under AD-inducing conditions, the MIND diet significantly reduced cortical Aβ and total tau by 41.9% and 22.7%, while the gluten-free diet significantly reduced them by 50.3% and 41.6%, relative to the AD disease-control group (all P < .001). Histopathologically, both diets preserved cortical and hippocampal architecture, but behaviorally, diet showed no significant effect on the novel object recognition discrimination index ( P = 0.092). Both the MIND and gluten-free diets successfully attenuated Aβ accumulation, tau pathology, and neurodegeneration in AlCl₃-induced AD models, with the gluten-free diet yielding greater numerical reductions.