Send to

Choose Destination
J Alzheimers Dis. 2015;46(4):989-1005. doi: 10.3233/JAD-143222.

Characterization of Cerebral Damage in a Monkey Model of Alzheimer's Disease Induced by Intracerebroventricular Injection of Streptozotocin.

Author information

National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Republic of Korea.
Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
Department of Biomedical Engineering, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Republic of Korea.


In line with recent findings showing Alzheimer's disease (AD) as an insulin-resistant brain state, a non-transgenic animal model with intracerebroventricular streptozotocin (icv-STZ) administration has been proposed as a representative experimental model of AD. Although icv-STZ rodent models of AD have been increasingly researched, studies in non-human primate models are very limited. In this study, we aimed to characterize the cerebral damage caused by icv-STZ in non-human primates; to achieve this, three cynomolgus monkeys (Macaca fascicularis) were administered four dosages of STZ (2 mg/kg) dissolved in artificial cerebrospinal fluid and another three controls were injected with only artificial cerebrospinal fluid at the cerebellomedullary cistern. In vivo neuroimaging was performed with clinical 3.0 T MRI, followed by quantitative analysis with FSL for evaluation of structural changes of the brain. Immunohistochemistry was performed to evaluate cerebral histopathology. We showed that icv-STZ caused severe ventricular enlargement and parenchymal atrophy, accompanying amyloid-β deposition, hippocampal cell loss, tauopathy, ependymal cell loss, astrogliosis, and microglial activation, which are observed in human aged or AD brain. The findings suggest that the icv-STZ monkey model would be a valuable resource to study the mechanisms and consequences of a variety of cerebral pathologies including major pathological hallmarks of AD. Furthermore, the study of icv-STZ monkeys could contribute to the development of treatments for age- or AD-associated cerebral changes.


Alzheimer’s disease; animal model; brain; monkey; streptozotocin

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for IOS Press
Loading ...
Support Center