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Using Retinal Imaging to Study Dementia
Published on: November 6, 2017
The capillary dysfunction hypothesis of Alzheimer's disease
Leif Østergaard1, Rasmus Aamand, Eugenio Gutiérrez-Jiménez
1Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark. leif@cfin.dk
Neurobiology of Aging
|October 23, 2012
Summary
Alzheimer's disease (AD) involves complex changes in cerebral blood flow (CBF). This review explains how altered capillary flow patterns cause both hypoperfusion and hyperperfusion in AD.
Area of Science:
- Neuroscience
- Physiology
- Pathology
Background:
- Alzheimer's disease (AD) pathogenesis is linked to hypoperfusion and capillary changes.
- Hyperperfusion in young, high-risk individuals presents a paradox with established AD pathology.
- Cerebral blood flow (CBF) coupling with metabolic needs may differ across disease stages.
Purpose of the Study:
- To explain the paradox of hyperperfusion and hypoperfusion in Alzheimer's disease (AD).
- To model cerebral oxygen availability considering capillary flow heterogeneity.
- To analyze the biphasic nature of CBF responses in preclinical and clinical AD.
Main Methods:
- Review of existing literature on AD, cerebral blood flow, and capillary morphology.
- Development of a model for cerebral oxygen availability incorporating capillary flow heterogeneity.
- Analysis of the model's predictions regarding CBF regulation.
Main Results:
- The model predicts that increased capillary heterogeneity initially requires elevated CBF for oxygenation.
- Progressive capillary heterogeneity leads to suppressed CBF to maintain metabolism under low oxygen tension.
- The biphasic CBF response in AD aligns with progressive capillary flow disturbances.
Conclusions:
- Progressive disturbances in capillary flow patterns explain the observed biphasic CBF changes in Alzheimer's disease.
- Capillary flow heterogeneity is a key factor in the etiopathogenesis of AD.
- Further research into sources of capillary flow heterogeneity is warranted.
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