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Neurobiol Aging. 2018 Feb;62:82-94. doi: 10.1016/j.neurobiolaging.2017.10.006. Epub 2017 Oct 16.

Disturbances in the control of capillary flow in an aged APPswe/PS1ΔE9 model of Alzheimer's disease.

Author information

1
Center of Functionally Integrative Neuroscience and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: eugenio@cfin.au.dk.
2
Center of Functionally Integrative Neuroscience and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
3
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
4
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
5
Center of Functionally Integrative Neuroscience and MINDLab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.

Abstract

Vascular changes are thought to contribute to the development of Alzheimer's disease, and both cerebral blood flow and its responses during neural activation are reduced before Alzheimer's disease symptoms onset. One hypothetical explanation is that capillary dysfunction reduces oxygen extraction efficacy. This study compares the morphology and hemodynamics of the microvasculature in the somatosensory cortex of 18-month-old APPSWE/PS1ΔE9 (transgenic [Tg]) mice and wild-type (WT) littermates. In particular, the extent to which their capillary transit times homogenize during functional activation was measured and compared. Capillary length density was similar in both groups but capillary blood flow during rest was lower in the Tg mice, indicating that cortical oxygen availability is reduced. The capillary hemodynamic response to functional activation was larger, and lasted longer in Tg mice than in WT mice. The homogenization of capillary transit times during functional activation, which we previously demonstrated in young mice, was absent in the Tg mice. This study demonstrates that both neurovascular coupling and capillary function are profoundly disturbed in aged Tg and WT mice.

KEYWORDS:

Alzheimer's disease; Capillary dysfunction; Capillary length density; Capillary transit time heterogeneity; Cerebral blood flow; Red blood cell velocity

[Indexed for MEDLINE]

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