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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 (naive) 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 ÊM 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.

Original languageEnglish
Article number011005
JournalNeurophotonics
Volume1
Issue number1
DOIs
StatePublished - Jul 1 2014

Keywords

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

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