Cerebral Aβ deposition in an Aβ-precursor protein-transgenic rhesus monkey.

• Type of Material: Article
• Authors: Anthony WS Chan, Emory University; In Ki Cho, Emory University; Chun-Xia Li, Emory University; Xiaodong Zhang, Emory University; Sudeep Patel, Emory University; Rebecca Rusnak, Emory University; Jessica Raper, Emory University; Jocelyne Bachevalier, Emory University; Sean P Moran, Emory University; Tim Chi, Emory University; Katherine H Cannon, Emory University; Carissa E Hunter, Emory University; Ryan Martin, Emory University; Haillian Xiao, Emory University; Shang-Hsun Yang, Emory University; Sanjeev Gumber, Emory University; James G Herndon, Emory University; Rebecca F Rosen, Emory University; William T Hu, Emory University; James Lah, Emory University; Allan Levey, Emory University; Yoland Smith, Emory University; Lary C Walker, Emory University
• Language: English
• Date: 2022
• Publisher: Elsevier BV
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nbas.2022.100044
• Title of Journal or Parent Work: Aging Brain
• Volume: 2
• Grant/Funding Information: Portions of this work were supported by National Institutes of Health (NIH) grants P50 AG025688, ORIP/OD P51 OD011132, and the Transgenic Huntington’s Disease Monkey Resource grant awarded by the ORIP/NIH (OD010930) to A.W.S.C. Neuropsychiatric behavioral assessments were supported by generous donations of the Arthur and Sarah Merrill Foundation.
• Keywords: Alzheimer’s disease; Amyloid precursor protein; Cerebral amyloid angiopathy; Tau; Animal model
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Nursing; Psychology, General

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.