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

Abstract

<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>β</mml:mi></mml:mrow> </mml:math> -Amyloid ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> ) plaque, representing the progressive accumulation of the protein that mainly consists of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> , is one of the prominent pathological hallmarks of Alzheimer's disease (AD). Label-free imaging of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> plaques holds the potential to be a histological examination tool for diagnosing AD. We applied label-free multiphoton microscopy to identify extracellular <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> plaque as well as intracellular <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> deposition, which demonstrated that both extracellular and intracellular <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>A</mml:mi> <mml:mi>β</mml:mi></mml:mrow> </mml:math> deposition by color coding. These results provide an approach for investigating pathophysiology of AD that can complement traditional biomedical procedures.