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© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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). This consortium will study gene-edited marmoset models carrying genetic risk for AD and wild-type genetically diverse aging marmosets from birth throughout their lifespan, using non-invasive longitudinal assessments. These include characterizing the genetic, molecular, functional, behavioral, cognitive, and pathological features of aging and AD.

Results

The consortium successfully generated viable founders carrying PSEN1 mutations in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community.

Discussion

By establishing marmoset models of AD, we will be able to investigate primate-specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.

Details

Title
Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease
Author
Sukoff Rizzo, Stacey J 1 ; Homanics, Gregg 1 ; Schaeffer, David J 1 ; Schaeffer, Lauren 1 ; Park, Jung Eun 1 ; Oluoch, Julia 1 ; Zhang, Tingting 1 ; Haber, Annat 2 ; Seyfried, Nicholas T 3 ; Paten, Benedict 4 ; Greenwood, Anna 5 ; Murai, Takeshi 1 ; Sang Ho Choi 1 ; Huhe, Hasi 1 ; Kofler, Julia 1 ; Strick, Peter L 1 ; Carter, Gregory W 2 ; Silva, Afonso C 1 

 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA 
 The Jackson Laboratory, Bar Harbor, Maine, USA 
 Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA 
 University of California Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, California, USA 
 Sage Bionetworks, Seattle, Washington, USA 
Section
PERSPECTIVE
Publication year
2023
Publication date
Jul 2023
Publisher
John Wiley & Sons, Inc.
ISSN
23528737
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2869147868
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.