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Neurophotonics. 2014 Jul;1(1):011005.

Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment.

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Beckman Laser Institute and Medical Clinic, Laser Microbeam and Medical Program, 1002 Health Sciences Road, Irvine, California 92612 ; University of California Irvine, Department of Biomedical Engineering, 3120 Natural Sciences II, Irvine, California 92697-2715.
Beckman Laser Institute and Medical Clinic, Laser Microbeam and Medical Program, 1002 Health Sciences Road, Irvine, California 92612.
University of California Irvine, Institute for Memory Impairments and Neurological Disorders, 2642 Biological Sciences III Irvine, California 92697-4545 ; University of California Irvine, Department of Neurobiology and Behavior, 2205 McGaugh Hall, Irvine, California 92697-4550.


Alzheimer's disease (AD) and cerebrovascular disease are often comorbid conditions, but the relationship between amyloid-β and in vivo vascular pathophysiology is poorly understood. We utilized a multimodal, multiscale optical imaging approach, including spatial frequency domain imaging, Doppler optical coherence tomography, and confocal microscopy, to quantify AD-dependent changes in a triple transgenic mouse model (3xTg-AD) and age-matched controls. From three months of age (naïve) to 20 months (severe AD), the brain tissue concentration of total and oxy-hemoglobin (Total Hb, ctO2Hb) decreased 50 and 70%, respectively, in 3xTg-AD mice. Compared to age-matched controls, significant differences in brain hemoglobin concentrations occurred as early as eight months (Total Hb: 126 ± 5 μM versus 108 ± 4 μM; ctO2Hb: 86 ± 5 μM versus 70 ± 3 μM; for control and AD, respectively). These changes were linked to a 29% vascular volume fraction decrease and 35% vessel density reduction in the 20-month-old 3xTg-AD versus age-matched controls. Vascular reduction coincided with increased brain concentration of amyloid-β protein, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) at eight and 20 months compared to the three-month baseline. Our results suggest that amyloid-β blocks the normally reparative effects of upregulated VEGF and eNOS, and may accelerate in vivo vascular pathophysiology in AD.


Doppler optical coherence tomography; absorption; diffuse optical spectroscopy; hypercapnia; microvascular perfusion; neuroimaging; scattering; spatial frequency domain imaging; vascular reactivity

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