Age-Dependent Effect of [beta]-Amyloid Toxicity on Basal Forebrain Cholinergic Neurons and Inflammation in the Rat Brain

Beta-amyloid (A[beta]) accumulation, neuroinflammation, basal forebrain cholinergic loss and hippocampal degeneration are well-described pathologies associated with Alzheimer's disease (AD). However, the role that age plays in the susceptibility of the brain to these AD pathologies and the relationships between them is still not well understood. This study investigated the age-related response to intracerebroventricular injection of A[beta]25-35 in 3-, 6- and 9-month-old rats. A[beta] toxicity resulted in an age-related increase in cholinergic loss and microglial activation in the basal forebrain along with neuronal loss in the hippocampal CA3 subfield. Performance in the Morris water maze revealed impairments in long-term reference memory in 6-month-old A[beta] administered animals, which was not seen in 3-month-old animals. These results support a role of A[beta] administration in inducing age-dependent cholinergic loss and neuroinflammation, and additionally provide evidence for a more age-appropriate model of adult-onset A[beta] toxicity demonstrating pathological changes that reflect the early stages of AD pathogenesis including neuroinflammation, cholinergic loss and beginning stages of memory impairment.