Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer's Disease

A hallmark of Alzheimer's disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (A beta) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated A beta may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis, any agent that has the capability to inhibit A beta aggregation and/or destroy amyloid plaques represents a potential disease-modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the A beta-soluble protofibrils was approved by the US FDA for AD therapy, thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo A beta aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms were widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in A beta aggregation seeding of the interactions between zinc ions, A beta with the isomerized Asp7 (isoD7-A beta) and the alpha 4 beta 2 nicotinic acetylcholine receptor.