Data Sheet 1_Platelets from early-stage Alzheimer patients show enhanced amyloid binding, an elevated open canalicular system and sex-specific differences in their activation profile.pdf

IntroductionAlzheimer's disease (AD) is associated with neurodegeneration and dementia. Key clinical hallmarksinclude the deposition of amyloid-ß (Aβ) into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA). Currently, anti-Aß antibodies are emerging as possible therapy for AD. Several biomarkers, such as Aß and tau-protein have gained diagnostic relevance for early AD; however, their assessment requires cerebrospinal fluid. Therefore, blood-based biomarkers for AD screening are urgently needed.
MethodsPatients diagnosed with early AD were analyzed for extracellular Aß binding to platelets, platelet morphology and platelet activation, and were compared with age-matched controls.
ResultsPlatelet number and size were unaltered between groups. However, platelets isolated from AD patients exhibited increased surface APP/Aβ immunoreactivity compared with age-matched controls. Transmission electron microscopy revealed altered platelet morphology in AD patients, including changes in the number of dense granules and an increased area of the open canalicular system (OCS). While only minor differences in platelet activation were detected between patients and controls, a significant reduction in integrin αIIbβ3 (fibrinogen receptor) activation was observed in platelets from female compared to male AD patients, as determined by flow cytometry.
ConclusionThe results presented here emphasize the importance of understanding whether platelets contribute to AD pathology in a sex-specific manner. Furthermore, platelet parameters may serve as promising biomarker for early AD prognosis, as platelets are easily accessible via blood sampling. These parameters may include sex-specific platelet activation profiles, the ability of platelets to bind APP/Aß at their surface, and OCS dimensions assessed by electron microscopy.

引言：阿尔茨海默病（Alzheimer's disease, AD）与神经退行性变及痴呆密切相关。其核心临床特征包括β淀粉样蛋白（amyloid-ß, Aβ）在脑实质内沉积形成老年斑，以及在脑血管中沉积引发脑淀粉样血管病（cerebral amyloid angiopathy, CAA）。目前，抗Aβ抗体已成为阿尔茨海默病潜在的治疗方案。多种生物标志物（如Aβ与tau蛋白）已在早期阿尔茨海默病的诊断中展现出应用价值，但此类标志物的检测需依赖脑脊液样本。因此，临床上亟需可用于阿尔茨海默病筛查的血液生物标志物。
方法：本研究对确诊为早期阿尔茨海默病的患者进行分析，检测其血小板结合细胞外Aβ的能力、血小板形态及血小板活化状态，并与年龄匹配的健康对照者进行对比。
结果：两组受试者的血小板计数及体积均无显著差异。然而，与年龄匹配的对照者相比，阿尔茨海默病患者分离得到的血小板其表面淀粉样前体蛋白（Amyloid Precursor Protein, APP）/Aβ免疫反应性显著升高。透射电子显微镜观察显示，阿尔茨海默病患者的血小板形态发生改变，包括致密颗粒数量变化以及开放管道系统（open canalicular system, OCS）面积增大。尽管两组间血小板活化仅存在微小差异，但通过流式细胞术检测发现，女性阿尔茨海默病患者的血小板整合素αIIbβ3（纤维蛋白原受体）活化水平显著低于男性患者。
结论：本研究结果凸显了探究血小板是否以性别特异性方式参与阿尔茨海默病病理进程的重要性。此外，由于血小板可通过血液采样便捷获取，血小板相关参数或可成为早期阿尔茨海默病预后评估的潜在生物标志物。此类参数可包括性别特异性的血小板活化特征、血小板表面结合APP/Aβ的能力，以及通过电子显微镜评估的OCS尺寸。