Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease
Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease
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DOI：
10.1038/s41598-019-53638-9
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发表时间：
2019-11-20
影响因子：
4.6
通讯作者：
Hortobagyi, Tibor
中科院分区：
文献类型：
--
作者：
Bencze, Janos;Szarka, Mate;Hortobagyi, Tibor
阿尔茨海默病（AD）和新皮质路易体病（LBD）是最常见的神经退行性痴呆，目前尚无有效的治疗方法。阐明病理机制和确定新的治疗靶点至关重要。狐猴酪氨酸激酶2（LMTK2）参与多种生理和病理细胞过程。因此，在AD和新皮质LBD样品中使用发色和荧光LMTK2免疫组织化学对死后脑组织进行神经病理学表征，并将其与年龄匹配的对照（CNT）进行比较。LMTK2免疫阳性仅限于神经元细胞质。神经元，包括tau蛋白阳性缠结轴承的，显示减少显色和免疫荧光标记在AD中的每一个皮质层相比，CNT和新皮质LBD。进行数字图像分析以测量各组的平均免疫阳性率。在测量每个单独神经元的灰度LMTK2信号强度后，计算每组的平均灰度值。CNT与AD和新皮质LBD与AD的平均灰度值之间存在显著差异。新皮质LBD的中度降低表明了共存AD病理学的影响。我们提供了神经病理学证据减少神经元LMTK2免疫标记AD，发病机制的影响。
Alzheimer's disease (AD) and neocortical Lewy body disease (LBD) are the most common neurodegenerative dementias, with no available curative treatment. Elucidating pathomechanism and identifying novel therapeutic targets are of paramount importance. Lemur tyrosine kinase 2 (LMTK2) is involved in several physiological and pathological cellular processes. Herewith a neuropathological characterization is presented in AD and neocortical LBD samples using chromogenic and fluorescent LMTK2 immunohistochemistry on post-mortem brain tissues and compared them to age-matched controls (CNTs). LMTK2 immunopositivity was limited to the neuronal cytoplasm. Neurons, including tau-positive tangle-bearing ones, showed decreased chromogenic and immunofluorescent labelling in AD in every cortical layer compared to CNT and neocortical LBD. Digital image analysis was performed to measure the average immunopositivity of groups. Mean grey values were calculated for each group after measuring the grey scale LMTK2 signal intensity of each individual neuron. There was significant difference between the mean grey values of CNT vs. AD and neocortical LBD vs. AD. The moderate decrease in neocortical LBD suggests the effect of coexisting AD pathology. We provide neuropathological evidence on decreased neuronal LMTK2 immunolabelling in AD, with implications for pathogenesis.