Augmentation of Sensory-Evoked Hemodynamic Response in an Early Alzheimer's Disease Mouse Model

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Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal hyperactivation has been proposed as an early marker for diagnosis of AD. The BOLD response results from neurovascular coupling, i.e., hemodynamic response induced by neuronal activity. However, there has been no evidence of task-induced increases in hemodynamic response in animal models of AD. Here, we observed an augmented hemodynamic response pattern in a transgenic A beta PPSWE/PS1 Delta E9 mouse model of AD using three in vivo imaging methods: intrinsic optical signal imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry. Sensory stimulation resulted in augmented and prolonged hemodynamic responses in transgenic mice evidenced by changes in total, oxygenated, and deoxygenated hemoglobin concentration. This difference between transgenic and wild-type mice was significant at 7 months of age when amyloid plaques and cerebral amyloid angiopathy had developed but not at younger or older ages. Correspondingly, sensory stimulation-induced pial arteriole diameter was also augmented and prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in transgenic mice was augmented but not prolonged. These results are consistent with the existence of BOLD signal hyperactivation in non-demented AD-risk human subjects, supporting its potential use as an early diagnostic marker of AD.
Publisher
IOS PRESS
Issue Date
2013-01
Language
English
Article Type
Article
Keywords

MILD COGNITIVE IMPAIRMENT; HIPPOCAMPAL ACTIVATION; GENETIC RISK; CEREBROVASCULAR DYSFUNCTION; SPECTROSCOPIC ANALYSIS; TRANSGENIC MICE; FMRI EVIDENCE; OLDER-ADULTS; MEMORY; BRAIN

Citation

JOURNAL OF ALZHEIMERS DISEASE, v.37, no.4, pp.857 - 868

ISSN
1387-2877
DOI
10.3233/JAD-121900
URI
http://hdl.handle.net/10203/187382
Appears in Collection
BiS-Journal Papers(저널논문)
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