Use of Ethological Rodent Behavior to Assess Efficacy of Potential Drugs for Alzheimer's Disease

Nest construction is a natural, species-typical behavior in rodents [1,2] that may be considered analogous to the “activities of daily living” disrupted in Alzheimer’s disease (AD) [3]. Assessment of species-typical home cage behaviors such as nesting in transgenic mice may aid in identifying drugs with potential for improving functional status in AD patients [4]. This strategy provides an alternative or addition to the standard preclinical assessment of cognitive function via maze learning. Most cognitive deficits in AD related transgenic mice occur later in life and are very time consuming to assess. Use of nesting would be a novel screening method. We used two methods to assess nest building; a rating scale based on subjective assessment of the nest quality and an objective grid counting system. We placed individual mice in cages with measured amounts of corn cob and an additional bedding material (Alpha Dri). Mice were left overnight and cages photographed the following morning for subsequent blind assessment of nest quality. Wildtype mice typically separated out and formed nests from the Alpha Dri material. This behavior was less evident in Tg2576 mice, which model AD-type amyloid beta-protein (As) neuropathology and in tg4510 mice, which carry a mutated human tau gene implicated in the fronto-temporal dementia. Since deficits in most behaviors do not occur until 6-18 months of age, using this early appearing behavior is advantageous.