Aging Brain (Jan 2022)
Cerebral Aβ deposition in an Aβ-precursor protein-transgenic rhesus monkey
- Anthony W.S. Chan,
- In Ki Cho,
- Chun-Xia Li,
- Xiaodong Zhang,
- Sudeep Patel,
- Rebecca Rusnak,
- Jessica Raper,
- Jocelyne Bachevalier,
- Sean P. Moran,
- Tim Chi,
- Katherine H. Cannon,
- Carissa E. Hunter,
- Ryan C. Martin,
- Hailian Xiao,
- Shang-Hsun Yang,
- Sanjeev Gumber,
- James G. Herndon,
- Rebecca F. Rosen,
- William T. Hu,
- James J. Lah,
- Allan I. Levey,
- Yoland Smith,
- Lary C. Walker
Affiliations
- Anthony W.S. Chan
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
- In Ki Cho
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Chun-Xia Li
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Xiaodong Zhang
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Sudeep Patel
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Rebecca Rusnak
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Jessica Raper
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
- Jocelyne Bachevalier
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Psychology, Emory College, Atlanta, GA 30322, USA
- Sean P. Moran
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Tim Chi
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Katherine H. Cannon
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Carissa E. Hunter
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Ryan C. Martin
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Hailian Xiao
- Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
- Shang-Hsun Yang
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
- Sanjeev Gumber
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- James G. Herndon
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- Rebecca F. Rosen
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA
- William T. Hu
- Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
- James J. Lah
- Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
- Allan I. Levey
- Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
- Yoland Smith
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
- Lary C. Walker
- Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA; Corresponding author at: Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
- Journal volume & issue
-
Vol. 2
p. 100044
Abstract
With the ultimate goal of developing a more representative animal model of Alzheimer's disease (AD), two female amyloid-β-(Aβ) precursor protein-transgenic (APPtg) rhesus monkeys were generated by lentiviral transduction of the APP gene into rhesus oocytes, followed by in vitro fertilization and embryo transfer. The APP-transgene included the AD-associated Swedish K670N/M671L and Indiana V717F mutations (APPSWE/IND) regulated by the human polyubiquitin-C promoter. Overexpression of APP was confirmed in lymphocytes and brain tissue. Upon sacrifice at 10 years of age, one of the monkeys had developed Aβ plaques and cerebral Aβ-amyloid angiopathy in the occipital, parietal, and caudal temporal neocortices. The induction of Aβ deposition more than a decade prior to its usual emergence in the rhesus monkey supports the feasibility of creating a transgenic nonhuman primate model for mechanistic analyses and preclinical testing of treatments for Alzheimer's disease and cerebrovascular amyloidosis.
