Neuroprotective Effects of Liraglutide and/or Rivastigmine Combination on the Rat Hippocampus

This study evaluated the neuroprotective potential of a combination therapy using liraglutide (LIRA), an antidiabetic agent, and rivastigmine (RIVA), a standard treatment for Alzheimer's disease (AD), in a rat model of aluminum chloride (AlCl₃)‐induced AD. Male rats were divided into five groups: control, AD (AlCl₃,75 mg/kg for 60 days), RIVA‐treated (1 mg/kg daily for 6 weeks), LIRA‐treated (300 µg/kg daily for 6 weeks), and combination‐treated (LIRA + RIVA). Cognitive function was assessed behaviorally, and hippocampal biomarkers related to AD—such as microtubule‐associated protein Tau (MAPt), Beta‐Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1), Sequestosome 1 (SQSTM1/p62), and acetylcholinesterase (AChE) activity—were evaluated. Histopathological changes, immunohistochemistry, and transmission electron microscopy were also assessed. The levels of MAPt, BACE1, SQSTM1/p62, and AChE in the LIRA + RIVA group were 11.32 ± 0.467 ng/mL, 1069 ± 80.1 pg/mL, 408.7 ± 19.41 pg/mL, and 0.805 ± 0.342 µmol of acetylthiocholine iodide hydrolyzed/min/g of tissue, respectively. These levels were significant ( p < 0.01) when compared with the AlCl 3 group. Histological findings supported these biochemical data, indicating enhanced neuroprotection. LIRA may have a potential neuroprotective effect due to the rise in AChE, BACE1, (SQSTM1/p62) amyloid beta (Aβ), and caspase‐3 levels induced by AlCl 3 . Co‐administration of LIRA and RIVA provided superior neuroprotective effects compared with RIVA alone, suggesting a promising therapeutic strategy for preserving cognitive function in AD.