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Am J Neurodegener Dis 2012;1(1):32-48

Review Article
Can zebrafish be used as animal model to study Alzheimer's disease?

Soraya Santana, Eduardo P Rico, Javier S Burgos

BioPharma Division, Neuron Bio, Parque Tecnológico de Ciencias de la Salud, Edificio BIC, Avda. de la Innovación 1,
18100 Armilla, Granada, Spain. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade
Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-Anexo, Porto Alegre, RS, Brazil.

Received April 16, 2012; accepted May 12, 2012; Epub May 15, 2012; published May 30, 2012

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. (AJND1104003)

Keywords: Zebrafish, Alzheimer’s disease, neurotoxins, cholinergic neurotransmission, glutamatergic
neurotransmission, GABAergic neurotransmission, apolipoprotein E, APP, presenilins, TAU

Address all correspondence to:
Dr. Javier S. Burgos
Neuron Bio, Parque Tecnológico de Ciencias de la Salud
Edificio BIC, Avda. de la Innovación 1, 18100 Armilla
Granada, Spain.
Phone: +34 958 750 598. Fax: +34 958 750 459
E-mail: jburgos@neuronbio.com