DEVELOPING A NON-HUMAN PRIMATE MODEL OF ALZHEIMER DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have succeeded in establishing the first transgenic primate models of Alzheimer's disease. We currently have two healthy female, germline amyloid precursor protein-transgenic rhesus monkeys, aged 41 (RQd12; AD-1) and 31 (RNn12; AD-2) months, and a 31-month-old male monkey (ROn12; AD-3) with mosaic integration of the transgene. These animals are now approaching breeding age, and the next critical stage of the project is to increase the number of transgenic animals, to confirm the germline transmissibility of the transgene, and to maintain baseline behavioral, cellular and neurobiological analyses in order to capture the emerging transgene-related phenotype of this unique model. The size, behavioral complexity and biological proximity to humans make the transgenic AD monkey ideal for the longitudinal study of early biomarkers and behavioral changes, imaging studies with magnetic resonance and selective radioligands, metabolic analysis of protein turnover, neuropathological evolution through brain biopsy, and testing of experimental therapeutic approaches such as stem cells or genetic therapy.