Cognitive and Histological Methodological Framework for an Intrahippocampal Aβ_1-42 Rat Model of Alzheimer's Disease

Standardized and ethically compliant animal models remain essential for improving translational research in Alzheimer's disease. Although Aβ_1-42-induced rodent models are widely used, methodological variability continues to limit reproducibility.

We explored the feasibility of a stereotactic intrahippocampal Aβ_1-42 rat model established by bilaterally injecting pre-aggregated peptide into the hippocampus of adult Sprague Dawley rats. Model feasibility and targeting accuracy were assessed intraoperatively. Cognitive performance was evaluated using the Y-maze for spatial recognition memory and the novel object recognition (NOR) test. Histological examination was performed using hematoxylin-eosin (H&E) and Congo red staining to assess cytoarchitecture and to provide supportive evidence of amyloid-like deposits.

The surgical procedure was well-tolerated, and the injected animals showed reduced performance in behavioural testing, including reduced spatial recognition memory in the Y-maze and decreased discrimination indices in the NOR test. The animals also showed histological changes, including Congo red-positive birefringent structures consistent with amyloid-like congophilic material.

This study presents a feasible experimental framework for intrahippocampal Aβ_1-42 administration, showing behavioural and histological changes under the present experimental conditions. However, further validation, including sham-operated controls and molecular characterization, will be required before these findings can be interpreted as specific to Aβ-driven pathology.