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Original Article
The study of susceptibility weighted imaging of amyloid plaques and iron deposits in the brain of APP/PS1 transgenic AD mice
LIU Hao-di  ZHENG Yang  WANG Xiao-ming 

DOI:10.12015/issn.1674-8034.2018.08.010.


[Abstract] Objective: The aim is to apply the three dimensional enhanced magnetic sensitive imaging (3D-enhanced susceptibility weighted angiography, ESWAN) technology to detect APPswe/PSEN1de9 gene mutant mice (purchased from the United States Jackson that referred to as APP/PS1 transgenic mice) average phase values from different parts of the brain (mean phase value, MPV), and to explore its and ferritin and correlation of the distribution of amyloid plaques.Materials and Methods: APP/PS1 mutant mice and wild-type control mice underwent T1WI, T2WI and ESWAN sequence scanning to measure MPV in the cerebral cortex, hippocampus and thalamus of mice. Immunohistochemical staining of iron protein and Aβ protein in rat brain tissues was carried out, and the percentage of the number and area of stained plaques in the area of interest were counted respectively. Pearson correlation was used to analyze the MPV, patch number and patch area percentage in the ROI region.Results: The MPV values in the cortex area (t=-2.201, P=0.045) and hippocampal area (t=-2.524, P=0.024) of both APP/PS1 dual-transgenic mice and control mice were statistically different. There was no statistically significant difference in MPV between APP/PS1 dual transgenic mice and control mice in thalamus region (t=-2.094, P=0.055). The number and range of iron protein plaques and MPV in each group of APP/PS1 dual-transgenic mice were significantly correlated (P<0.05). The amount and range of amyloid plaques and ferritin were correlated (P<0.05).Conclusions: The mean phase value in the brain of transgenic mice with APP/PS1 was significantly correlated with iron deposition in the brain. The iron deposition in the cerebral cortex, hippocampus and thalamus continued in the APP/PS1 dual transgenic mice, and was associated with the formation of amyloid plaques.
[Keywords] 3D-enhanced susceptibility weighted angiography;Mean phase value;Mice, transgenic;Amyloid plaques;Ferritin;Magnetic resonance imaging

LIU Hao-di Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China

ZHENG Yang Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China

WANG Xiao-ming* Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China

*Correspondence to: Wang XM, E-mail: wangxm024@163.com

Conflicts of interest   None.

ACKNOWLEDGMENTS  This work was part of National Natural Science Foundation of China No. 81471720 Subsidized Project of Liaoning Provincial Education Department No. LZ2014039 and Outstanding Scientific Fund of Shengjing Hospital No. 201402
Received  2018-03-13
Accepted  2018-06-08
DOI: 10.12015/issn.1674-8034.2018.08.010
DOI:10.12015/issn.1674-8034.2018.08.010.

[1]
Thal DR, Attems J, Ewers M, et al. Spreading of amyloid, tau, and microvascular pathology in Alzheimer's disease: findings from neuropathological and neuroimaging studies. J Alzheimers Dis, 2014, 42 (Suppl 4): 421-429.
[2]
Liu C, Li W, Tong KA, et al. Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain. J Magn Reson Imaging, 2015, 42(1): 23-41.
[3]
Westland DJ, Mihailovic D, Ryan JF, et al. Characterization of in vivo MRI detectable thalamic amyloid plaques from APP/PS1 mice. Neurobiol Aging, 2009, 30(1): 41-53.
[4]
Langkammer C, Krebs N, Goessler W, et al. Quantitative MR imaging of brain iron: a postmortem validation study T2 values in the human brain: comparison with quantitative assays of iron and ferritin. Radiology, 2010, 257(2): 455-462.
[5]
Wang D, Li YY, Luo JH, et al. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imagingAge distribution and iron dependency of the T2-relaxation time in the globus pallidus and putamen. Arch Gerontol Geriatr, 2014, 59(2): 439-449.
[6]
Yan S, Sun J, Chen Y, et al. Brain iron deposition in white matter hyperintensities: a 3-T MRI study Imaging iron stores in the brain using magnetic resonance imaging. Age (Dordr), 2013, 35(5): 1927-1936.
[7]
Meadowcroft MD, Connor JR, Smith MB, et al. MRI and histological analysis of beta-amyloid plaques in both human Alzheimer's disease and APP/PS1transgenic mice. J Magn Reson Imaging, 2009, 29(5): 997-1007.
[8]
Bartzokis G, Tishler TA, Lu PH, et al. Brain ferritin iron may influence age- and gender-related risks of neuro degeneration. Neurobiol Aging, 2007, 28(3): 414-423.
[9]
Gao L, Jiang Z, Cai Z, et al. Brain iron deposition analysis using susceptibility weighted imaging and its association with body iron level in patients with mild cognitive impairment. Mol Med Rep, 2017, 16(6): 8209-8215.
[10]
Bertram L, Lill CM, Tanzi RE. The genetics of Alzheimer disease: back to the future. Neuron, 2010, 68(2): 270-281.
[11]
Timmer NM, van Dijk L, van der Zee CE, et al. Enoxaparin treatment administered at both early and late stages of amyloid β deposition improves cognition of APPswe/PS1dE9 mice with differential effects on brain Aβ levels. Neurobiol Dis, 2010, 40(1): 340-347.
[12]
Izco M, Martínez P, Corrales A, et al. Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Neuroscience, 2014, 263: 269-279.
[13]
Ferguson SA, Sarkar S, Schmued LC. Longitudinal behavioral changes in the APP/PS1 transgenic Alzheimer's disease model. Behav Brain Res, 2013, 242(1): 125-134.
[14]
Koralewski M, Balejčíková L, Mitróová Z, et al. Morphology and magnetic structure of the ferritin core during iron loading and release by magnetooptical and NMR methods. ACS Appl Mater Interfaces, 2018, 10(9): 7777-7787.
[15]
Uddin MN, Lebel RM, Wilman AH, et al. Value of transverse relaxometry difference methods for iron in human brain field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores. Magn Reson Imaging, 2016, 34(1): 51-59.
[16]
Telling ND, Everett J, Collingwood JF, et al. Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer's disease. Cell Chem Biol, 2017, 24(10): 1205-1215.
[17]
Zhu WZ, Zhong WD, Wang W, et al. Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease. Radiology, 2009, 253(2): 497-504.
[18]
Lee Y, Han Y, Park H. A new susceptibility-weighted image reconstruction method for the reduction of background phase artifacts. Magn Reson Med, 2014, 71(3): 1324-1335.
[19]
Aquino D, Bizzi A, Grisoli M, et al. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology, 2009, 252(1): 165-172.
[20]
Lupton MK, Benyamin B, Proitsi P, et al. No genetic overlap between circulating iron levels and Alzheimer's disease. J Alzheimers Dis, 2017, 59(1): 85-99.
[21]
Wang D, Li WB, Wei XE, et al. An investigation of age-related iron deposition using susceptibility weighted imaging. PLoS One, 2012, 7(11): e50706.

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