REVIEW: Role of Interaction between Zinc and Amyloid Beta in Pathogenesis of Alzheimer’s Disease

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Sergey A. Kozin^a

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

Received August 24, 2022; Revised October 3, 2022; Accepted October 5, 2022

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Progression of Alzheimer’s disease is accompanied by the appearance of extracellular deposits in the brain tissues of patients with characteristic supramolecular morphology (amyloid plaques) the main components of which are β-amyloid isoforms (Aβ) and biometal ions (zinc, copper, iron). For nearly 40 years and up to the present time, the vast majority of experimental data indicate critical role of formation and accumulation of amyloid plaques (cerebral amyloidogenesis) in pathogenesis of Alzheimer’s disease, however, nature of the molecular agents that initiate cerebral amyloidogenesis, as well as causes of aggregation of the native Aβ molecules in vivo remained unknown for a long time. This review discusses the current level of fundamental knowledge about the molecular mechanisms of interactions of zinc ions with a number of Aβ isoforms present in amyloid plaques of the patients with Alzheimer’s disease, and also shows how this knowledge made it possible to identify driving forces of the cerebral amyloidogenesis in Alzheimer’s disease and made it possible to determine fundamentally new biomarkers and drug targets as part of development of innovative strategy for diagnosis and treatment of Alzheimer’s disease.

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KEY WORDS: Alzheimer’s disease, amyloid-β, zinc complex, oligomerization, amyloid plaques, biomarker, drug target

DOI: 10.1134/S0006297923140055

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