Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.
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Conference Article|
July 20 2011
Axon–glial disruption: the link between vascular disease and Alzheimer's disease?
Karen Horsburgh
;
Karen Horsburgh
1
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
1To whom correspondence should be addressed (email karen.horsburgh@ed.ac.uk).
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Michell M. Reimer
;
Michell M. Reimer
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
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Philip Holland
;
Philip Holland
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
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Guiquan Chen
;
Guiquan Chen
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
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Gillian Scullion
;
Gillian Scullion
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
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Jill H. Fowler
Jill H. Fowler
1
Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Cognitive and Neural Systems, 1 George Square, University of Edinburgh, EH8 9JZ, U.K.
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Biochem Soc Trans (2011) 39 (4): 881-885.
Article history
Received:
December 06 2010
Citation
Karen Horsburgh, Michell M. Reimer, Philip Holland, Guiquan Chen, Gillian Scullion, Jill H. Fowler; Axon–glial disruption: the link between vascular disease and Alzheimer's disease?. Biochem Soc Trans 1 August 2011; 39 (4): 881–885. doi: https://doi.org/10.1042/BST0390881
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