Label-free multiphoton imaging of β-amyloid plaques in Alzheimer's disease mouse models.

Shu Wang,Jianxin Chen,Bingbing Lin,Caihong Sun,Xingfu Wang,Ruolan Lin,Lidian Chen,Yunkun Wu,Jia Huang,Jing Tao,Guimin Lin

doi:10.1117/1.nph.6.4.045008

Abstract

.-Amyloid () plaque, representing the progressive accumulation of the protein that mainly consists of , is one of the prominent pathological hallmarks of Alzheimer’s disease (AD). Label-free imaging of plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular plaque as well as intracellular accumulation for the first time from AD mouse models. We showed that a two-photon-excited fluorescence signal is a sensitive optical marker for revealing the spatial–temporal progression and the surrounding morphological changes of deposition, which demonstrated that both extracellular and intracellular accumulations play an important role in the progression of AD. Moreover, combined with a custom-developed image-processing program, we established a rapid method to visualize different degrees of deposition by color coding. These results provide an approach for investigating pathophysiology of AD that can complement traditional biomedical procedures.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by decline of memory, learning, thinking, and other cognitive functions and is the most common cause of dementia in the elderly.[1]
We demonstrated the capability of label-free multiphoton microscopy (MPM) to visualize extracellular and intracellular Aβ accumulations in brain tissue from the APP/PS1 and APP/PS1/Tau transgenic mouse model of AD
We focused on the spatial– temporal progression and the surrounding morphological changes of Aβ deposition, demonstrating that both extracellular and intracellular Aβ accumulations play an important pathophysiological role in the progression of AD

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by decline of memory, learning, thinking, and other cognitive functions and is the most common cause of dementia in the elderly.[1]. The clinical imaging technique of positron emission tomography (PET) is able to image Aβ deposits in transgenic mouse models and humans in vivo after intravenous administration of tracer Pittsburgh compound B.5,6. Magnetic resonance imaging has been demonstrated to visualize in vivo individual AD plaques without the use of a contrast agent in transgenic mice, showing great promise for imaging Aβ plaques in living human Alzheimer patients noninvasively.[7] these techniques are limited by low spatial resolution, and PET depends on radioactive ligands, in only trace amounts. Some groups have observed autofluorescence and second-harmonic generation (SHG) at senile plaques by multiphoton microscopy (MPM),[15,16] they only have imaged extracellular Aβ plaques in the hippocampal regions of elderly mice, and they are unable to reveal brain-wide mapping of plaque distribution and intracellular Aβ accumulation

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Discussion

Conclusion