Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's disease mouse model.
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 AβPP(SWE)/PS1ΔE9 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.
Laboratory for Cognitive Neuroscience and NeuroImaging, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
Jinho
J
Kim
Yong
Y
Jeong
D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D042241:Early Diagnosis; D004558:Electric Stimulation / Q000379:methods; D006439:Hemodynamics / Q000502:physiology*; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D011984:Sensory Receptor Cells / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
Alzheimer's disease; cerebral amyloid angiopathy; functional brain imaging; multiphoton fluorescence microscopy