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

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

Author information

1
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.
2
Beckman Laser Institute and Medical Clinic, Laser Microbeam and Medical Program, 1002 Health Sciences Road, Irvine, California 92612.
3
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.

Abstract

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.

KEYWORDS:

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

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