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The capillary dysfunction hypothesis of Alzheimer's disease

Authors :
Østergaard, Leif
Aamand, Rasmus
Gutiérrez-Jiménez, Eugenio
Ho, Yi-Ching L.
Blicher, Jakob U.
Madsen, Søren M.
Nagenthiraja, Kartheeban
Dalby, Rikke B.
Drasbek, Kim R.
Møller, Arne
Brændgaard, Hans
Mouridsen, Kim
Jespersen, Sune N.
Jensen, Morten S.
West, Mark J.
Source :
Neurobiology of Aging. Apr2013, Vol. 34 Issue 4, p1018-1031. 14p.
Publication Year :
2013

Abstract

Abstract: It is widely accepted that hypoperfusion and changes in capillary morphology are involved in the etiopathogenesis of Alzheimer''s disease (AD). This is difficult to reconcile with the hyperperfusion observed in young high-risk subjects. Differences in the way cerebral blood flow (CBF) is coupled with the local metabolic needs during different phases of the disease can explain this apparent paradox. This review describes this coupling in terms of a model of cerebral oxygen availability that takes into consideration the heterogeneity of capillary blood flow patterns. The model predicts that moderate increases in heterogeneity requires elevated CBF in order to maintain adequate oxygenation. However, with progressive increases in heterogeneity, the resulting low tissue oxygen tension will require a suppression of CBF in order to maintain tissue metabolism. The observed biphasic nature of CBF responses in preclinical AD and AD is therefore consistent with progressive disturbances of capillary flow patterns. Salient features of the model are discussed in the context of AD pathology along with potential sources of increased capillary flow heterogeneity. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
01974580
Volume :
34
Issue :
4
Database :
Academic Search Index
Journal :
Neurobiology of Aging
Publication Type :
Academic Journal
Accession number :
84743138
Full Text :
https://doi.org/10.1016/j.neurobiolaging.2012.09.011