Mondal Rommani, Sandhu Yasmin K, Kamalia Vallabhi M, Delaney Brooke A, Syed Amina U, Nguyen Grace A H, Moran Taylor R, Limpengco Roz R, Liang Christopher, Mukherjee Jogeshwar
Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
Biomedicines. 2023 Mar 27;11(4):1033. doi: 10.3390/biomedicines11041033.
High-resolution scans of immunohistochemical (IHC) stains of Alzheimer's disease (AD) brain slices and radioligand autoradiography both provide information about the distribution of Aβ plaques and Tau, the two common proteinopathies in AD. Accurate assessment of the amount and regional location of Aβ plaques and Tau is essential to understand the progression of AD pathology. Our goal was to develop a quantitative method for the analysis of IHC-autoradiography images. Postmortem anterior cingulate (AC) and corpus callosum (CC) from AD and control (CN) subjects were IHC stained with anti-Aβ for Aβ plaques and autoradiography with [F]flotaza and [I]IBETA for Aβ plaques. For Tau, [I]IPPI, a new radiotracer, was synthesized and evaluated in the AD brain. For Tau imaging, brain slices were IHC stained with anti-Tau and autoradiography using [I]IPPI and [I]IPPI. Annotations for Aβ plaques and Tau using QuPath for training and pixel classifiers were generated to measure the percent of the area of Aβ plaques and Tau in each slice. The binding of [I]IPPI was observed in all AD brains with an AC/CC ratio > 10. Selectivity to Tau was shown by blocking [I]IPPI with MK-6240. Percent positivity for Aβ plaques was 4-15%, and for Tau, it was 1.3 to 35%. All IHC Aβ plaque-positive subjects showed [F]flotaza and [I]IBETA binding with a positive linear correlation (r > 0.45). Tau-positive subjects showed [I]IPPI binding with a stronger positive linear correlation (r > 0.80). This quantitative IHC-autoradiography approach provides an accurate measurement of Aβ plaques and Tau within and across subjects.
阿尔茨海默病（AD）脑切片的免疫组织化学（IHC）染色高分辨率扫描和放射性配体放射自显影均提供有关Aβ斑块和Tau分布的信息，这是AD中两种常见的蛋白病。准确评估Aβ斑块和Tau的数量及区域位置对于理解AD病理学进展至关重要。我们的目标是开发一种用于分析IHC-放射自显影图像的定量方法。对AD和对照（CN）受试者的死后前扣带回（AC）和胼胝体（CC）进行免疫组织化学染色，使用抗Aβ抗体检测Aβ斑块，并使用[F]flotaza和[I]IBETA进行Aβ斑块的放射自显影。对于Tau，合成了一种新的放射性示踪剂[I]IPPI并在AD脑中进行评估。对于Tau成像，脑切片用抗Tau进行免疫组织化学染色，并使用[I]IPPI和[I]IPPI进行放射自显影。使用QuPath生成用于训练和像素分类器的Aβ斑块和Tau注释，以测量每个切片中Aβ斑块和Tau的面积百分比。在所有AC/CC比率>10的AD脑中均观察到[I]IPPI的结合。用MK-6240阻断[I]IPPI显示出对Tau的选择性。Aβ斑块的阳性百分比为4-15%，Tau的阳性百分比为1.3至35%。所有免疫组织化学Aβ斑块阳性受试者均显示[F]flotaza和[I]IBETA结合，呈正线性相关（r>0.45）。Tau阳性受试者显示[I]IPPI结合，呈更强的正线性相关（r>0.80）。这种定量的免疫组织化学-放射自显影方法可在个体内部和个体之间准确测量Aβ斑块和Tau。
