Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments.
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October 2017
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In this issue of Clinical Science, Thompson et al (pages 2489-2501) describe their research on the capacity of protein tyrosine phosphatase 1B inhibitor to reverse atherosclerotic plaque formation in a mouse model. The cover image shows aortic root sections of mice fed on a high-fat-diet that are stained with Oil Red - a method the authors used to quantify plaque formation in this study.
Review Article|
September 28 2017
Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia
Jessica Duncombe;
Jessica Duncombe
*
1Centre for Neuroregeneration, University of Edinburgh, Edinburgh, U.K.
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Akihiro Kitamura;
Akihiro Kitamura
*
1Centre for Neuroregeneration, University of Edinburgh, Edinburgh, U.K.
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Yoshiki Hase;
Yoshiki Hase
*
2National Cerebral and Cardiovascular Center, Osaka, Japan
3Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.
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Masafumi Ihara;
Masafumi Ihara
2National Cerebral and Cardiovascular Center, Osaka, Japan
3Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.
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Raj N. Kalaria;
Raj N. Kalaria
2National Cerebral and Cardiovascular Center, Osaka, Japan
3Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.
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Karen Horsburgh
2National Cerebral and Cardiovascular Center, Osaka, Japan
3Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.
Correspondence: Karen Horsburgh ([email protected])
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Publisher: Portland Press Ltd
Received:
May 05 2017
Revision Received:
August 28 2017
Accepted:
September 04 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (19): 2451–2468.
Article history
Received:
May 05 2017
Revision Received:
August 28 2017
Accepted:
September 04 2017
Citation
Jessica Duncombe, Akihiro Kitamura, Yoshiki Hase, Masafumi Ihara, Raj N. Kalaria, Karen Horsburgh; Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin Sci (Lond) 1 October 2017; 131 (19): 2451–2468. doi: https://doi.org/10.1042/CS20160727
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