Cumulative data suggest the involvement of Fyn tyrosine kinase in Alzheimer's disease (AD). Previously, our group has shown increased immunoreactivities of the FynT isoform in AD neocortex (with no change in the alternatively spliced FynB isoform) which associated with neurofibrillary degeneration and reactive astrogliosis. Since both the aforementioned neuropathological features are also variably found in Lewy Body dementias (LBD), we investigated potential perturbations of Fyn expression in the post‐mortem neocortex of patients with AD, as well as those diagnosed as having one of the two main subgroups of LBD: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). We found selective upregulation of FynT expression in AD, PDD, and DLB which also correlated with cognitive impairment. Furthermore, increased FynT expression correlated with hallmark neuropathological lesions, soluble β‐amyloid, and phosphorylated tau, as well as markers of microglia and astrocyte activation. In line with the human post‐mortem studies, cortical FynT expression in aged mice transgenic for human P301S tau was upregulated and further correlated with accumulation of aggregated phosphorylated tau as well as with microglial and astrocytic markers. Our findings provide further evidence for the involvement of FynT in neurodegenerative dementias, likely via effects on tauopathy and neuroinflammation.

中文翻译：

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FynT 激酶表达的异构体特异性上调与阿尔茨海默病和路易体痴呆中的 tau 蛋白病和神经胶质细胞激活有关

累积数据表明 Fyn 酪氨酸激酶与阿尔茨海默病 (AD) 有关。此前，我们的研究小组已经证明 AD 新皮质中 FynT 同工型的免疫反应性增加（选择性剪接的 FynB 同工型没有变化），这与神经原纤维变性和反应性星形胶质细胞增生有关。由于上述两种神经病理学特征在路易体痴呆 (LBD) 中也有所不同，因此我们研究了 AD 患者死后新皮质中 Fyn 表达的潜在扰动，以及那些被诊断为患有 AD 的两个主要亚组之一的患者。 LBD：帕金森病痴呆（PDD）和路易体痴呆（DLB）。我们发现 AD、PDD 和 DLB 中 FynT 表达选择性上调，这也与认知障碍相关。此外，FynT 表达增加与标志性神经病理病变、可溶性 β-淀粉样蛋白和磷酸化 tau 蛋白以及小胶质细胞和星形胶质细胞激活标记物相关。与人类尸检研究一致，人 P301S tau 转基因老年小鼠的皮质 FynT 表达上调，并进一步与聚集的磷酸化 tau 积累以及小胶质细胞和星形胶质细胞标记物相关。我们的研究结果为 FynT 参与神经退行性痴呆提供了进一步的证据，可能是通过对 tau 蛋白病和神经炎症的影响。