Cellular and animal model

Background: Alzheimer's disease (AD), the most common dementing disorder of late life, is a major cause of disability and death in the elderly. Neurobiological, genetic, and molecular studies have defined the vulnerable neural systems, abnormalities in cytoskeletal proteins in neurons, the biology of the β-amyloid precursor protein (APP) and β-amyloid (Aβ, βA4), and several APP mutations linked to the disease. More recently, investigators have begun to develop animal models essential for delineating pathogenetic mechanisms and for developing and testing new therapies for treating AD in humans. Methods: Animal Exposure: In 1980 − 81, a cohort of female monkeys (Macaca fascicularis) was randomly assigned at birth to one of two exposure groups: one received 1.5 mg/kg/day of lead acetate (Pb) from birth until 400 days of age via infant formula and vehicle after weaning, while the other group served as a control group and received formula or vehicle only. Results: Pb levels: The exposure of these animals to low level of inorganic Pb from birth to 400 days resulted in blood Pb levels of 19 − 26 μg/dL when being dosed with Pb after weaning from infant formula. Conclusions: Exposure of cultured mouse primary neurons to these peptides confirmed that both of these peptides were toxic to the cells even in the soluble form and that Aβ1 − 42 was more cytotoxic than Aβ1 − 40.