Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary.
Sci Rep. 2019 Nov 20;9(1):17222. doi: 10.1038/s41598-019-53638-9.
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.
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症，目前尚无有效的治疗方法。阐明发病机制和寻找新的治疗靶点至关重要。狐猴酪氨酸激酶 2（LMTK2）参与了多种生理和病理细胞过程。本研究通过对死后脑组织进行显色和荧光 LMTK2 免疫组织化学染色，对 AD 和新皮质 LBD 样本进行了神经病理学特征描述，并将其与年龄匹配的对照组（CNT）进行了比较。LMTK2 免疫阳性仅限于神经元细胞质。与 CNT 和新皮质 LBD 相比，AD 患者的每个皮质层中，包括 tau 阳性缠结的神经元在内，其显色和免疫荧光标记均减少。进行了数字图像分析，以测量各组的平均免疫阳性率。在测量每个神经元的 LMTK2 信号强度的灰度值后，计算每组的平均灰度值。CNT 与 AD 以及新皮质 LBD 与 AD 之间的平均灰度值存在显著差异。新皮质 LBD 的中度减少表明存在共存的 AD 病理学的影响。我们提供了 AD 中神经元 LMTK2 免疫标记减少的神经病理学证据，这对发病机制具有重要意义。
