This Notice of Funding Opportunity (NOFO) supports the optimization of promising genome editing-based therapeutic leads for Alzheimer's Disease-Related Dementias (ADRD), towards IND-enabling studies. Specifically, it supports the characterization and optimization of therapeutic lead(s) that show promise as potential genome editing therapeutics, as evidenced by convincing proof-of-concept studies in appropriate models. At the end of the funding period, successful projects will have optimized a genome editing therapeutic candidate with demonstrated bioactivity, manufacturability, biodistribution, in vivo efficacy, and/or target engagement (measurement of proximal downstream effects) and optimal dosing, combined with other properties consistent with the desired clinical application. This NOFO is not specific for any one or group within the ADRD spectrum of disorders. Disorders include; Frontotemporal dementia (FTD), Lewy body dementias (LBD) (including Dementia with Lewy bodies (DLB), Parkinson Disease Dementia (PDD)), Vascular contributions to Cognitive Impairment and Dementia (VCID), and Multiples Etiology Dementias (MED).