Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.

Abstract

Alzheimer's disease (AD) is not a single-cause disease; rather, it is a complex neurodegenerative disease involving multiple pathological pathways influenced by various risk factors. Aggregation and accumulation of amyloid beta (Aβ) and tau are the most prominent features in the brains of AD patients. Aggregated Aβ and tau exert neurotoxic effects in the central nervous system, contributing to the pathogenesis and progression of AD. They also act synergistically to cause neurodegeneration, resulting in memory loss. In this context, dual inhibition of Aβ and tau aggregation, or dissociation of these two aggregates, is considered promising for AD treatment. Recently, dual inhibitors capable of simultaneously targeting the aggregation and dissociation of both Aβ and tau have been investigated. Specific amino acid domains of Aβ and tau associated with their aggregation/dissociation have been identified. Subsequently, therapeutic agents that prevent aggregation or promote disaggregation by targeting these domains have been identified/developed. In this review, we summarize the major domains and properties involved in Aβ and tau aggregation, as well as the therapeutic effects and mechanisms of agents that simultaneously regulate their aggregation and dissociation. This comprehensive review may contribute to the design and discovery of next-generation dual-targeting drugs for Aβ and tau, potentially leading to the development of more effective therapeutic strategies for AD.