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Published on: March 16, 2016
Repeated Intra-cisterna Magna Injections with Amyloid-beta Oligomers to Induce Alzheimer's Disease in Cynomolgus
Jiyeon Cho1, Jinyoung Won1, Yu Gyeong Kim1,2
1National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.
Abstract:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder which results in cognitive decline and memory loss, characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain. Despite numerous efforts to develop animal models of AD across various species to understand its pathological characteristics and underlying mechanisms, the model that accurately mimics the pathological phenotypes of AD remains elusive. In this study, we aimed to induce sporadic AD pathological progression in non-human primates (NHP) through the repeated administration of Aβ oligomers (AβO) via the CBCT-guided intra-cisterna manga (ICM) injection. Cynomolgus monkeys were administered AβO twice a week for four weeks, and then euthanized one week after the final injection. We found that AβO-injected NHP developed AD pathologies, including Aβ deposition, synaptic impairment, and neuroinflammation in the CA1 area of the hippocampus. Additionally, the levels of hyperphosphorylated tau were significantly increased in the cerebrospinal fluid (CSF) of AβO-injected NHP. Our results demonstrate that repeated AβO injection via the ICM route induces several early-stage AD-like neuropathological alterations, including intracellular Aβ accumulation, tau phosphorylation, and synaptic dysfunction. The present study indicates that repeated ICM administration of AβO could be good approach to reproduce a translational NHP model of AD, enabling the study of AD pathogenesis and pre-clinical testing of potential therapeutic candidates for AD.
Insights
Researchers developed a new non-human primate model for Alzheimer's disease (AD) by injecting amyloid beta oligomers (AβO). This model shows key AD pathologies, aiding future research and therapeutic testing.
Area of Science:
- Neuroscience
- Neuropathology
- Primate Models
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder causing cognitive decline, marked by amyloid beta (Aβ) plaques and neurofibrillary tangles.
- Current animal models often fail to fully replicate AD's complex pathology, hindering research and drug development.
Purpose of the Study:
- To establish a non-human primate (NHP) model that mimics sporadic Alzheimer's disease progression.
- To investigate the neuropathological effects of repeated amyloid beta oligomer (AβO) administration in cynomolgus monkeys.
Main Methods:
- Cynomolgus monkeys received repeated intra-cisterna magna (ICM) injections of AβO over four weeks.
- Neuropathological assessments were performed post-mortem, focusing on the hippocampus and cerebrospinal fluid (CSF).
Main Results:
- AβO-injected NHPs exhibited key AD pathologies, including Aβ deposition and neuroinflammation in the hippocampus.
- Synaptic impairment and increased hyperphosphorylated tau levels in CSF were observed in the NHP model.
- The study successfully induced early-stage AD-like changes, such as intracellular Aβ accumulation and tau phosphorylation.
Conclusions:
- Repeated ICM administration of AβO effectively induces early-stage Alzheimer's-like neuropathology in NHPs.
- This NHP model provides a valuable platform for studying AD pathogenesis and evaluating potential therapies.
