Rabbit as an Animal Model of Alzheimer's Disease

As a result of the rarity of spontaneous Alzheimer’s disease (AD) development in non-human species, animal models mimicking various aspects of this disease have only recently been innovated – typically via dietary, pharmacological, or genetic manipulations. Of these new experimental AD models, the rabbit hypercholesterolemia model, originally developed for the study of atherosclerosis (described above), has a variety of advantages that make it one of the leading models for AD research as well. [1]

Physiologically at the cellular and molecular levels, rabbits fed high-cholesterol diets display many of the neuropathologies observed in humans with AD. The brains of these rabbits show increased levels of cholesterol and Amyloid β (Aβ) and decreased levels of acetylcholine, increased Aβ, tau, and ApoE immunoreactivity, Aβ plaques in the extracellular space, a breakdown in the blood-brain barrier, and an increase in microglial and decrease in neuronal cell populations. The phylogenetic proximity of rabbits and humans is reflected in the 97% amino acid sequence conservation observed between the two species’ Aβ proteins and is a major advantage over other models of AD including fruit flies, mice, and rats. Anatomically, rabbits have larger brains relative to the aforementioned species allowing for greater flexibility in testing for cognitive impairment. Cognitively, rabbits with hypercholesterolemia-induced AD display age-dependent deficits in associative learning that closely parallel those observed in humans. As measured by impairment of eyeblink classical conditioning, these deficits are beyond those observed with normal aging, are specific to AD (i.e., not observed in Parkinson’s Disease or Huntington’s disease), and are relieved upon administration of drugs that improve cognition. No other experimental animal model of AD boasts such an extensive body of existing data by which to judge cognitive impairment as the classically-conditioned eye blink response of rabbits. [1]

Reference1. Woodruff-Pak, D.S. (2008) Animal models of Alzheimer’s disease: therapeutic implications. J. Alzheimers Dis. 15(4):507-521.