The Impact of Menhaden Fish Oil on Brain Tauopathy in Streptozotocin-Lipopolysaccharide-Induced Rodent Model of Alzheimer’s Disease

Background: Tauopathies, including Alzheimer’s disease (AD), are neurodegenerative conditions characterized by the accumulation of abnormally phosphorylated tau protein, often exacerbated by comorbid metabolic disorders such as diabetes mellitus. This study evaluated the neuroprotective effect of Menhaden Fish Oil (MFO), a rich source of preformed omega-3 fatty acids, on tau pathology in a streptozotocin-lipopolysaccharide (STZ-LPS)-induced rat model that mimics diabetes-associated AD. Methods: Thirty male Wistar rats were grouped into five distinct groups and subjected to treatment with either normal saline or MFO (1 g/kg or 3 g/kg) for 21 days, followed by biochemical, immunofluorescence microscopy, and RT-qPCR analyses. Results: MFO administration significantly reduced total tau protein levels and tau hyperphosphorylation at Ser202 in both the cortex and hippocampus. It also upregulated AKT-1 expression while downregulating GSK-3 and CASP-3, suggesting modulation of the AKT/GSK-3 signaling pathway. Conclusions: These findings demonstrate that MFO supplementation mitigates tau pathology and neuronal apoptosis in a metabolic-inflammatory model of AD, supporting its potential as a dietary neuroprotective strategy.