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

Alexander J. Lin; Gangjun Liu; Nicholas A. Castello; James J. Yeh; Rombod Rahimian; Grace Lee; Victoria Tsay; Anthony J. Durkin; Bernard Choi; Frank M. LaFerla; Zhongping Chen; Kim N. Green; Bruce J. Tromberg

doi:10.1117/1.NPh.1.1.011005

28 May 2014 Optical imaging in an Alzheimer’s mouse model reveals amyloid-β-dependent vascular impairment

Alexander J. Lin, Gangjun Liu, Nicholas A. Castello, James J. Yeh, Rombod Rahimian, Grace Lee, Victoria Tsay, Anthony J. Durkin, Bernard Choi, Frank M. LaFerla, Zhongping Chen, Kim N. Green, Bruce J. Tromberg

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Neurophotonics, Vol. 1, Issue 1, 011005 (May 2014). https://doi.org/10.1117/1.NPh.1.1.011005

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, ctO 2 Hb ) 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.

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Alexander J. Lin, Gangjun Liu, Nicholas A. Castello, James J. Yeh, Rombod Rahimian, Grace Lee, Victoria Tsay, Anthony J. Durkin, Bernard Choi, Frank M. LaFerla, Zhongping Chen, Kim N. Green, and Bruce J. Tromberg "Optical imaging in an Alzheimer’s mouse model reveals amyloid-β-dependent vascular impairment," Neurophotonics 1(1), 011005 (28 May 2014). https://doi.org/10.1117/1.NPh.1.1.011005

Published: 28 May 2014

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