Koch-Paszkowski Joanna, Sennett Christopher, Pula Giordano
Biomedical Institute of Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK.
Cells. 2025 Jul 12;14(14):1069. doi: 10.3390/cells14141069.
BACKGROUND/OBJECTIVES: A growing body of evidence is amassing in the literature suggesting a correlation between Alzheimer's disease (AD) and thrombotic vascular complications, which led to the suggestive hypothesis that thrombosis may contribute to AD onset and progression by damaging the neurovasculature and reducing the cerebral blood flow. In turn, low cerebral blood flow is likely to contribute to neurodegeneration by reducing nutrient and oxygen supply and impairing toxic metabolite removal from the brain tissue.
We searched the literature for studies in animal models of AD or patients diagnosed with the disease that reported circulating markers of platelet hyperactivity or hypercoagulation, or histological evidence of brain vascular thrombosis.
Platelet hyperactivity and hypercoagulability have been described in multiple animal models of AD, and histological evidence of neurovascular thrombosis has also been reported. Similarly, clinical studies on patients with AD showed circulating markers of platelet hyperactivity and hypercoagulation, or histological evidence of neurovascular thrombosis collected from post-mortem brain tissue samples.
Taken together, a convincing picture is emerging that suggests a strong correlation between systemic or neurovascular thrombosis and AD. Nonetheless, a mechanistic role for haemostasis dysregulation and neurovascular damage in the onset or the progression of AD remains to be proven. Future research should focus on this important question in order to clarify the mechanisms underlying AD and identify a treatment for this disease.
背景/目的：文献中积累的证据越来越多，表明阿尔茨海默病（AD）与血栓性血管并发症之间存在关联，这引发了一个推测性假设，即血栓形成可能通过损害神经血管系统和减少脑血流量，从而导致AD的发生和进展。反过来，低脑血流量可能通过减少营养物质和氧气供应以及损害从脑组织中清除有毒代谢产物，进而导致神经退行性变。
我们在文献中搜索了关于AD动物模型或已确诊患者的研究，这些研究报告了血小板活性亢进或高凝状态的循环标志物，或脑血管血栓形成的组织学证据。
在多种AD动物模型中均描述了血小板活性亢进和高凝状态，并且也报道了神经血管血栓形成的组织学证据。同样，针对AD患者的临床研究显示，存在血小板活性亢进和高凝状态的循环标志物，或从尸检脑组织样本中收集到的神经血管血栓形成的组织学证据。
综上所述，一个令人信服的情况正在显现，表明全身或神经血管血栓形成与AD之间存在密切关联。尽管如此，止血功能失调和神经血管损伤在AD发病或进展中的机制作用仍有待证实。未来的研究应关注这个重要问题，以阐明AD的潜在机制并确定该疾病的治疗方法。
