This NOFO would support development and validation of novel clinically- and/or pathophysiologically-relevant human cellular models of ADRD. The cellular model systems would be expected to capture the multi-faceted pathologies and multiple cell types observed in ADRDs. Validation includes internal, face, construct, and predictive (to the extent possible) validation. These models can be developed/validated with the goal of supporting therapy development or better understanding of human disease mechanisms and mechanisms that uncover predisposition to developing neurodegenerative dementias. Human cellular models need to be novel, complex, and address a gap in the currently available models. Multidisciplinary teams will be highly encouraged. Leveraging the use of and depositing new cells into existing NIH cell repository resources will also be encouraged.