Towards Better and More Valid Zebrafish Models of Alzheimer's Disease: A Scientific Tribute to Prof. Mikhail I. Aghajanov

The most common form of dementia, Alzheimer's disease (AD) is a severely debilitating neurodegenerative disorder that afflicts over 50 million people globally. Despite extensive its research using various animal models, nearly all promising AD treatments have failed in clinical trials. Zebrafish (Danio rerio) have recently emerged as a valuable alternative to traditional (rodent) models of AD, possessing conserved neurotransmitter systems and disease pathways with humans, as well as orthologs for key genes associated with neurodegenerative disease. Here, we review recent advances and applications of zebrafish to study the pathogenesis of AD, and discuss the advantages, limitations, and potential future directions of research utilizing zebrafish AD models. This paper is dedicated to the late Professor Mikhail I. Aghajanov (1939–2024), a prominent Armenian neurochemist and a true crusader for fundamental AD research. (Figure presented.)