PET applications in animal models of neurodegenerative and neuroinflammatory disorders

Studies on hereditary neurological disorders such as familial Alzheimer’s disease (AD) have revealed abnormalities of pathogenic proteins causative of neurodegeneration, while molecular initiators of sporadic neuropsychiatric conditions remain unidentified. Such disorders are characterized by collections of molecular abnormalities that may be critically involved in synaptic dysfunctions and other deteriorations in neurons. Diverse classes of radiochemicals designed for positron emission tomographic (PET) imaging facilitate delineation of mechanistic links among key molecules in these processes by tracking their spatiotemporal correlations. This assay technique is of particular utility when applied to rodent and nonhuman primate models given their suitability for invasive genetic and pharmacological interventions. In addition, the detection of neurochemical and neuropathological changes by PET can be examined in laboratory animals when combined with invasive antemortem and postmortem investigations such as in vivo microdialysis, electrophysiological and histopathological techniques. This review primarily covers the use of small animal models of brain disorders using PET to elucidate etiological molecular cascades to facilitate in turn the search for diagnostic and therapeutic agents applicable to AD and related disorders in humans.