Advances in neural mechanisms and magnetic resonance imaging biomarkers of aluminum exposure causing cognitive impairment.

Aluminum (Al) is the most widely distributed neurotoxic metallic element in the environment, and prolonged exposure can lead to cognitive impairment and increase the risk of developing Alzheimer's disease (AD). This article systematically reviews the critical mechanisms underlying aluminum-induced neurotoxicity: mediating neuronal apoptosis through activation of oxidative stress pathways and induction of mitochondrial dysfunction; engaging programmed cell death modalities such as necroptosis via activation of the RIP1/RIP3/MLKL signaling pathway; disrupting the homeostasis of neurotransmitter systems including glutamatergic and cholinergic pathways; and impairing synaptic plasticity. Neuroimaging studies demonstrate that magnetic resonance imaging (MRI) has revealed significant gray matter volume reduction in the hippocampus and frontal lobes of aluminum-exposed individuals, accompanied by disrupted functional connectivity in the default mode network (DMN) and diminished white matter integrity. Magnetic resonance spectroscopy (MRS) analyses indicate neuronal metabolic disturbances, while quantitative susceptibility mapping (QSM) further demonstrates abnormal cerebral iron deposition. These pathological manifestations may synergistically interact with β-amyloid (Aβ) protein aberrant aggregation and neurofibrillary tangles (NFTs) formation mediated by tau protein hyperphosphorylation. Although multimodal MRI techniques provide a crucial approach for dynamic monitoring of aluminum neurotoxicity, the research on its specific biomarker system requires further refinement. By conducting an in-depth exploration of the neural mechanisms underlying cognitive impairment induced by aluminum exposure and evaluating the feasibility of MRI-based imaging techniques as biomarkers for assessing aluminum neurotoxicity, this study aims to establish a theoretical foundation for early warning of cognitive dysfunction and development of targeted intervention strategies.