Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no cure and no effective diagnostic criteria. The greatest challenge in effectively treating AD is identifying biomarkers specific for each patient when neurodegenerative processes have not yet begun, an outcome that would allow the design of a personalised therapeutic approach for each patient and the monitoring of the therapeutic response during the treatment. We found that the excessive phosphorylation of the amyloid precursor protein (APP) Tyr₆₈₂ residue on the APP ₆₈₂YENPTY₆₈₇ motif precedes amyloid β accumulation and leads to neuronal degeneration in AD neurons. We proved that Fyn tyrosine kinase elicits APP phosphorylation on Tyr₆₈₂ residue, and we reported increased levels of APP Tyr₆₈₂ and Fyn overactivation in AD neurons. Here, we want to contemplate the possibility of using fibroblasts as tools to assess APP Tyr₆₈₂ phosphorylation in AD patients, thus making the changes in APP Tyr₆₈₂ phosphorylation levels a potential diagnostic strategy to detect early pathological alterations present in the peripheral cells of AD patients’ AD brains.

中文翻译：

---

阿尔茨海默病患者的成纤维细胞可能反映大脑病理学吗？关注淀粉样前体蛋白 Tyr682 残基磷酸化的增加

阿尔茨海默病（AD）是一种毁灭性的神经退行性疾病，无法治愈，也没有有效的诊断标准。有效治疗 AD 的最大挑战是在神经退行性过程尚未开始时识别每个患者特有的生物标志物，这一结果将允许为每个患者设计个性化的治疗方法并在治疗期间监测治疗反应。我们发现，淀粉样蛋白前体蛋白 (APP) APP ₆₈₂ YENPTY _{687基序上的 Tyr 682}残基过度磷酸化先于淀粉样蛋白 β 积累，并导致 AD 神经元中的神经元变性。我们证明 Fyn 酪氨酸激酶可引发 APP Tyr ₆₈₂残基磷酸化，并且我们报告了AD 神经元中APP Tyr ₆₈₂水平增加和 Fyn 过度激活。在这里，我们想要考虑使用成纤维细胞作为评估 AD 患者 APP Tyr _{682磷酸化的工具的可能性，从而使 APP Tyr 682}磷酸化水平的变化成为检测 AD 患者外周细胞中存在的早期病理改变的潜在诊断策略' AD 大脑。