Abstract: Zebrafish is rapidly emerging as a promising model organism to study various central nervous system (CNS)
disorders, including Alzheimer’s disease (AD). AD is the main cause of dementia in the human population and there is
an urgency to understand the causes of this neurodegenerative disease. In this respect, the development of new
animal models to study the underlying neurodegenerative mechanisms of AD is an urgent need. In this review we
analyze the current situation in the use of zebrafish as a model for AD, discussing the reasons to use this experimental
paradigm in CNS investigation and analyzing the several strategies adopted to induce an AD-like pathology in zebrafish.
We discuss the strategies of performing interventions to cause damage in the zebrafish brain by altering the
major neurotransmitter systems (such as cholinergic, glutamatergic or GABAergic circuits). We also analyze the several
transgenic zebrafish constructed for the AD study, discussing both the familial-AD models based on APP processing
pathway (APP and presenilins) and in the TAU hyperphosphorylation, together with the genes involved in sporadic-
AD, as apolipoprotein E. We conclude that zebrafish is in a preliminary stage of development in the AD field, and that
the transgenic animals must be improved to use this fish as an optimal model for AD research. Furthermore, a
deeper knowledge of the zebrafish brain and a better characterization of the injury caused by alterations in the major
neurotransmitter systems are needed.