A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis

Jang Hun Kim; Ho Young Kang; Sung Young Park; Yoo Mi Yang; Sang Kyung Jo; Dongho Geum; Jong Hoon Kim; Dong Hyuk Park

doi:10.3346/jkms.2025.40.e236

A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis

Jang Hun Kim, Ho Young Kang, Sung Young Park, Yoo Mi Yang, Sang Kyung Jo, Dongho Geum, Jong Hoon Kim, Dong Hyuk Park^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e236
Journal	Journal of Korean medical science
Volume	40
Issue number	35
DOIs	https://doi.org/10.3346/jkms.2025.40.e236
Publication status	Published - 2025 Sept 8

Bibliographical note

Publisher Copyright:
© 2025 The Korean Academy of Medical Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

Alzheimer’s Disease
Bilateral Carotid Artery Stenosis
Chronic Cerebral Hypoperfusion
Mixed Dementia
Vascular Dementia

ASJC Scopus subject areas

General Medicine

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10.3346/jkms.2025.40.e236

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title = "A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis",

abstract = "Background: Alzheimer{\textquoteright}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{\textquoteright}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.",

keywords = "Alzheimer{\textquoteright}s Disease, Bilateral Carotid Artery Stenosis, Chronic Cerebral Hypoperfusion, Mixed Dementia, Vascular Dementia",

author = "Kim, \{Jang Hun\} and Kang, \{Ho Young\} and Park, \{Sung Young\} and Yang, \{Yoo Mi\} and Jo, \{Sang Kyung\} and Dongho Geum and Kim, \{Jong Hoon\} and Park, \{Dong Hyuk\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Korean Academy of Medical Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.",

year = "2025",

month = sep,

day = "8",

doi = "10.3346/jkms.2025.40.e236",

language = "English",

volume = "40",

journal = "Journal of Korean medical science",

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T1 - A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis

AU - Kim, Jang Hun

AU - Kang, Ho Young

AU - Park, Sung Young

AU - Yang, Yoo Mi

AU - Jo, Sang Kyung

AU - Geum, Dongho

AU - Kim, Jong Hoon

AU - Park, Dong Hyuk

N1 - Publisher Copyright: © 2025 The Korean Academy of Medical Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

PY - 2025/9/8

Y1 - 2025/9/8

N2 - 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.

AB - 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.

KW - Alzheimer’s Disease

KW - Bilateral Carotid Artery Stenosis

KW - Chronic Cerebral Hypoperfusion

KW - Mixed Dementia

KW - Vascular Dementia

UR - https://www.scopus.com/pages/publications/105015795336

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DO - 10.3346/jkms.2025.40.e236

M3 - Article

C2 - 40923509

AN - SCOPUS:105015795336

SN - 1011-8934

VL - 40

JO - Journal of Korean medical science

JF - Journal of Korean medical science

IS - 35

M1 - e236

ER -

A Novel Mouse Model of Mixed Dementia Using Chronic Cerebral Hypoperfusion Induced by Bilateral Carotid Artery Stenosis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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