The Convergence of Alzheimer’s Disease Pathogenesis Concepts

Resumo

Advances in the research of molecular factors involved in the onset and progression of Alzheimer’s disease, have led to the creation of several pathogenesis concepts of the most common neurodegenerative disease in the world, and amyloid, cholinergic, and neuroinflammatory hypotheses became leading. Over past twenty years, based on these hypotheses, hundreds of drug prototypes were developed, but none of them were able to stop the development of Alzheimer’s disease. In this review, based on the latest experimental data on structure-function properties of chemically modified amyloid-beta isoforms, the concept of the origin and the mechanism of action of amyloid-beta with isomerized Asp7 residue, as a molecular agent of Alzheimer’s disease pathogenesis, is presented. This concept makes it possible not only to combine the most important aspects of existing hypotheses but also indicates ways of creating agents for fighting Alzheimer’s disease with a principally new mechanism of action, “disease-modifying drugs.”