Assessing the Effects of Acute Amyloid ß Oligomer Exposure in the Rat.

ABSTRACT

Alzheimer's disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid ß oligomers (AßO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AßO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aß, microglia, and cholinergic neurons. Rats exposed to AßO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aß was only observed in the corpus callosum surrounding the lateral ventricles. AßO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AßO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AßO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.