Toward a Molecular Framework of Systemic Multi-Organ Toxicity Induced by Chronic Aluminum Chloride Exposure

Aluminum chloride (AlCl₃) is widely used in experimental toxicology, particularly in rodent models of neurodegeneration, where its effects have been studied primarily in the central nervous system. However, experimental findings also indicate that chronic exposure is associated with changes across multiple peripheral organs, although these observations are often considered separately. In this review, we bring together evidence from different organ systems to examine aluminum toxicity from a broader perspective. Rather than focusing on isolated tissue-specific effects, we consider the extent to which reported findings may reflect overlapping molecular disturbances expressed across physiological systems. Within this context, organ-level outcomes are discussed as potentially related manifestations of shared underlying processes, while acknowledging variability in experimental conditions and model interpretation. To structure this synthesis, we outline a conceptual framework that links recurring molecular responses, system-level regulatory influences, and tissue-specific patterns of injury. This approach is intended to provide a more integrated way of organizing existing data rather than to establish a single unifying mechanism. Importantly, the pathological alterations discussed throughout this review are interpreted as experimentally observed toxicological manifestations of chronic AlCl₃ exposure rather than evidence that aluminum constitutes a definitive etiological cause of Alzheimer’s disease. Overall, this review aims to complement existing neuro-focused interpretations of the AlCl₃ model by situating it within a multi-organ context and highlighting areas where further integrative investigation may be warranted.