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 journalArticle

21 Citations (Scopus)

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 (US)
Article number011005
JournalNeurophotonics
Volume1
Issue number1
DOIs
StatePublished - Jul 1 2014
Externally publishedYes

Fingerprint

Optical Imaging
Amyloid
Blood Vessels
Alzheimer Disease
Nitric Oxide Synthase Type III
Vascular Endothelial Growth Factor A
Brain
Hemoglobins
Amyloidogenic Proteins
Cerebrovascular Disorders
Optical Coherence Tomography
Confocal Microscopy
Transgenic Mice

Keywords

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

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neuroscience (miscellaneous)

Cite this

Lin, A. J., Liu, G., Castello, N. A., Yeh, J. J., Rahimian, R., Lee, G., ... Tromberg, B. J. (2014). Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment. Neurophotonics, 1(1), [011005]. https://doi.org/10.1117/1.NPh.1.1.011005

Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment. / Lin, Alexander J.; Liu, Gangjun; Castello, Nicholas A.; Yeh, James J.; Rahimian, Rombod; Lee, Grace; Tsay, Victoria; Durkin, Anthony J.; Choi, Bernard; Laferla, Frank M.; Chen, Zhongping; Green, Kim N.; Tromberg, Bruce J.

In: Neurophotonics, Vol. 1, No. 1, 011005, 01.07.2014.

Research output: Contribution to journalArticle

Lin, AJ, Liu, G, Castello, NA, Yeh, JJ, Rahimian, R, Lee, G, Tsay, V, Durkin, AJ, Choi, B, Laferla, FM, Chen, Z, Green, KN & Tromberg, BJ 2014, 'Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment', Neurophotonics, vol. 1, no. 1, 011005. https://doi.org/10.1117/1.NPh.1.1.011005
Lin, Alexander J. ; Liu, Gangjun ; Castello, Nicholas A. ; Yeh, James J. ; Rahimian, Rombod ; Lee, Grace ; Tsay, Victoria ; Durkin, Anthony J. ; Choi, Bernard ; Laferla, Frank M. ; Chen, Zhongping ; Green, Kim N. ; Tromberg, Bruce J. / Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment. In: Neurophotonics. 2014 ; Vol. 1, No. 1.
@article{ed7ff90b7d394003b5803edc47d386a3,
title = "Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment",
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 {\^E}M 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 = "absorption, diffuse optical spectroscopy, Doppler optical coherence tomography, hypercapnia, microvascular perfusion, neuroimaging, scattering, spatial frequency domain imaging, vascular reactivity",
author = "Lin, {Alexander J.} and Gangjun Liu and Castello, {Nicholas A.} and Yeh, {James J.} and Rombod Rahimian and Grace Lee and Victoria Tsay and Durkin, {Anthony J.} and Bernard Choi and Laferla, {Frank M.} and Zhongping Chen and Green, {Kim N.} and Tromberg, {Bruce J.}",
year = "2014",
month = "7",
day = "1",
doi = "10.1117/1.NPh.1.1.011005",
language = "English (US)",
volume = "1",
journal = "Neurophotonics",
issn = "2329-4248",
publisher = "SPIE",
number = "1",

}

TY - JOUR

T1 - Optical imaging in an Alzheimer's mouse model reveals amyloid-β-dependent vascular impairment

AU - Lin, Alexander J.

AU - Liu, Gangjun

AU - Castello, Nicholas A.

AU - Yeh, James J.

AU - Rahimian, Rombod

AU - Lee, Grace

AU - Tsay, Victoria

AU - Durkin, Anthony J.

AU - Choi, Bernard

AU - Laferla, Frank M.

AU - Chen, Zhongping

AU - Green, Kim N.

AU - Tromberg, Bruce J.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - 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.

AB - 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.

KW - absorption

KW - diffuse optical spectroscopy

KW - Doppler optical coherence tomography

KW - hypercapnia

KW - microvascular perfusion

KW - neuroimaging

KW - scattering

KW - spatial frequency domain imaging

KW - vascular reactivity

UR - http://www.scopus.com/inward/record.url?scp=84978926995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978926995&partnerID=8YFLogxK

U2 - 10.1117/1.NPh.1.1.011005

DO - 10.1117/1.NPh.1.1.011005

M3 - Article

VL - 1

JO - Neurophotonics

JF - Neurophotonics

SN - 2329-4248

IS - 1

M1 - 011005

ER -