This is an administrative supplement request (PA-18-591) in response to NOT-AG-18-008 Disease focused (Alzheimer's and its related Dementias (AD/ADRD)-focused Administrative supplements for NIH grants that are not on Alzheimer's disease) to our ongoing NIH grant1R01AG052986-01A1 entitled ?In vivo and in vitro systems to validate geronic proteins and their mechanisms of action?. This project aims to deliver new insights into the possibility of rejuvenation by circulating substances using animal models. There are no Alzheimer's Disease-related studies proposed in this grant. In cohorts grant. We AD/ADRD structurally pursue Macaque response to NOT-AG-18-008, we request funds to scan of aged and younger non-human primates currently studied at Yale with the support of the parent We have l ongitudinal cognitive testing data on these Rhesus Macaques going back to the late 1990s. suggest that these animals represent a unique resource that can enhance therapy development for because age, cognition and the proposed imaging can be used to establish a unique, functional and analogous model of AD/ADRD. If successful, these animals will provide a unique platform to mechanistic studies on AD/ADRD by the research community at large and validate the Rhesus as an NHP model in AD/ADRD research. We propose the application of 3 Positron Emission Tomography (PET) tracers to image the evolution of dementia-like brain biomarkers in aging nonhuman primates (NHP). Specifically, we will image the development of amyloid plaque with 11C-PIB and tau protein with 18F-MK6240; these 2 tracers have been in widespread clinical use. In addition, we will use the novel synaptic density marker (11C-UCB-J) for the synaptic vesicle glycoprotein 2A (SV2A), which is expressed ubiquitously in synaptic vesicles, and is thus a marker of synaptic density. This is an entirely unique combination of in vivo imaging biomarkers and can uniquely be performed at Yale. When combined with the unique nonhuman primate (NHP) population at Yale, it opens the possibility to follow the evolution of dementia biomarkers in a way not possible with human subjects.
| Dodd, Garron T; Michael, Natalie J; Lee-Young, Robert S et al. (2018) Insulin regulates POMC neuronal plasticity to control glucose metabolism. Elife 7: |
| Stoiljkovic, Milan; Kelley, Craig; Horvath, Tamas L et al. (2018) Neurophysiological signals as predictive translational biomarkers for Alzheimer's disease treatment: effects of donepezil on neuronal network oscillations in TgF344-AD rats. Alzheimers Res Ther 10:105 |
