Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

Introduction: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan.

Methods: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.

Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease.

Introduction: Our limited understanding of the mechanisms that trigger the emergence of Alzheimer's disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that the development of a non-human primate model of AD will be an essential step toward overcoming limitations of other model systems and is crucial for investigating primate-specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD.

Methods: A new consortium has been established with funding support from the National Institute on Aging aimed at the generation, characterization, and validation of Marmosets As Research Models of AD (MARMO-AD).