Experimental basis for generating nonhuman primate models of frontotemporal dementia and Alzheimer's disease

To our knowledge, no reports have described nonhuman primate (NHP) models of frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) that do not depend on an overexpression paradigm. Based on our recent success in generating single human MAPT knock-in mouse models of FTDP-17, we describe the experimental basis for generating knock-in marmoset models of FTDP-17. In addition, successful generation of mutant PSEN1 knock-in marmoset models lacking exon 9 (PSEN1-Δ9) of Alzheimer's disease (AD) indicates that we will be able to reconstitute two major pathological features of AD, i.e., amyloid plaques and neurofibrillary tangles, in an accelerated manner by combining these models.