The use of Aged Monkeys to Study PD: Important Roles in Pathogenesis and Experimental Therapeutics

This chapter discusses use of aged monkeys for studying Parkinson's disease (PD). Monkeys are closer to humans phylogenetically and display a motor repertoire similar to humans. As a function of age, monkeys display crucial pathological and behavioral features that mimics PD. The data presented in the chapter illustrate that aged monkeys provide a unique model to study specific aspects of PD pathogenesis. Monkey models provide an important behavioral and morphological association with PD and provide an important resource to evaluate disease pathogenesis and a forum to test new symptomatic therapeutic strategies. Aged monkeys display motor deficits that are associated with a loss of dopamine phenotype independent of the loss of nigral neurons. This occurs early in the pathogenic cascade in PD. The loss of phenotype seen in aged monkeys is associated specifically with the accumulation of α-synuclein, a phenomenon also associated with the loss of dopaminergic markers in PD. The chapter also discusses about the observation that the nigrostriatal system in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP fails to compensate for the loss of dopaminergic function in a manner similar to that seen in young monkeys treated with MPTP.