Related Experiment Video
Updated: Jan 18, 2026
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery
Jang Hun Kim1,2, Ho-Young Kang1,2, Sung Young Park1,2
1Department of Neurosurgery, Korea University Anam Hospital, College of Medicine, Korea University, Seoul, Korea.
Background:
Alzheimer's disease (AD) and vascular dementia (VaD) have distinct pathognomonic features, but they frequently co-occur as mixed dementia (MD) in elderly adults. This study aimed to develop a novel MD mouse model using bilateral carotid artery stenosis (BCAS) in 5 times familial Alzheimer's disease (5xFAD) transgenic mice and characterize its behavioral and histological features.
Methods:
Thirteen C57BL/6 and sixteen 5xFAD transgenic mice were prepared. Six C57BL/6 and seven 5xFAD transgenic mice underwent BCAS surgery, and all mice were housed for 3 months. Mice were divided into wild-type (n = 7), VaD (n = 6), AD (n = 9), and MD (n = 7) groups. Neurobehavioral tests, including the Y-maze test (YMT) and passive avoidance test (PAT), along with immunohistochemical analysis of amyloid β plaque (6E10) and myelin basic protein, were performed.
Results:
MD mice exhibited similar deficits in YMT as AD and VaD groups but had significantly worse performance in PAT compared to all other groups. Histologically, MD mice showed amyloid-β accumulation in the cortex/hippocampus and axonal degeneration in the corpus callosum.
Conclusion:
This novel MD model demonstrates key features of both AD and VaD, providing a valuable tool for studying the pathophysiology of mixed dementia and testing potential therapeutic interventions.
Insights
A new mixed dementia (MD) mouse model was created using bilateral carotid artery stenosis in 5xFAD mice. This model shows combined Alzheimer's disease and vascular dementia features, aiding research into MD treatments.
Area of Science:
- Neuroscience
- Pathology
- Animal Models
Background:
- Alzheimer's disease (AD) and vascular dementia (VaD) often co-occur as mixed dementia (MD) in older adults.
- Distinct pathological features of AD and VaD present challenges in studying MD.
- Developing accurate animal models is crucial for understanding MD pathophysiology.
Purpose of the Study:
- To develop and characterize a novel mouse model of mixed dementia (MD).
- The model was created by applying bilateral carotid artery stenosis (BCAS) to 5xFAD transgenic mice.
- To evaluate the behavioral and histological outcomes of this new MD model.
Main Methods:
- Utilized C57BL/6 and 5xFAD transgenic mice.
- BCAS surgery was performed on a subset of mice.
- Mice were housed for 3 months, followed by neurobehavioral tests (Y-maze, passive avoidance) and immunohistochemical analysis (amyloid-β, myelin basic protein).
Main Results:
- MD mice exhibited cognitive deficits in the Y-maze test, comparable to AD and VaD groups.
- MD mice showed significantly impaired performance in the passive avoidance test compared to other groups.
- Histological analysis revealed amyloid-β plaque accumulation and axonal degeneration in MD mice.
Conclusions:
- The novel BCAS-treated 5xFAD mouse model effectively replicates key features of both AD and VaD.
- This model serves as a valuable tool for investigating the underlying mechanisms of mixed dementia.
- The model can be used to test the efficacy of potential therapeutic strategies for MD.
