Aluminum and Alzheimer's disease in the 21st century: An umbrella review of evidence and controversies.

Identificador:  imarina:9597315

Handle: https://hdl.handle.net/20.500.11797/imarina9597315

Autors:  Domingo JL; Colomina MT

Resum:
The potential role of aluminum (Al) in the onset and progression of Alzheimer disease (AD) remains among the most enduring and divisive controversies in environmental neurotoxicology. Although numerous narrative reviews, systematic reviews, meta-analyses, mechanistic appraisals, and toxicological assessments have been published, their conclusions remain heterogeneous and at times contradictory. The present review of reviews critically integrates the PubMed-indexed review literature published in this century (January 1, 2000, and May 2, 2026), focusing on epidemiology, exposure sources, toxicokinetics, biological plausibility, experimental models, biomarkers, preventive measures, and unresolved methodological challenges. A predefined selection strategy was applied, prioritizing reviews that directly addressed Al and AD, employed systematic or meta-analytic approaches, examined epidemiological or mechanistic evidence, evaluated exposure assessment, or offered influential conceptual frameworks. Peripheral reviews were considered only when they provided essential context. The methodological quality of the included reviews was appraised qualitatively, considering transparency of the search strategy, reproducibility of methods, consideration of bias, and relevance to the review objectives. The strength of the evidence supporting each main conclusion was graded as strong, moderate, or limited. The evidence reviewed indicates that Al can promote several AD-related biological processes in experimental settings, including oxidative stress, mitochondrial dysfunction, neuroinflammation, glial activation, disrupted calcium signaling, amyloid beta aggregation, impaired amyloid clearance, tau phosphorylation, autophagy impairment, and epigenetic alterations. Epidemiological findings a