Walker Lauren, Attems Johannes
Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK.
J Parkinsons Dis. 2024;14(1):35-52. doi: 10.3233/JPD-230154.
Pathologies characteristic of Alzheimer's disease (i.e., hyperphosphorylated tau and amyloid-β (Aβ) plaques), cardiovascular disease, and limbic predominant TDP-43 encephalopathy (LATE) often co-exist in patients with Parkinson's disease (PD), in addition to Lewy body pathology (α-synuclein). Numerous studies point to a putative synergistic relationship between hyperphosphorylation tau, Aβ, cardiovascular lesions, and TDP-43 with α-synuclein, which may alter the stereotypical pattern of pathological progression and accelerate cognitive decline. Here we discuss the prevalence and relationships between common concomitant pathologies observed in PD. In addition, we highlight shared genetic risk factors and developing biomarkers that may provide better diagnostic accuracy for patients with PD that have co-existing pathologies. The tremendous heterogeneity observed across the PD spectrum is most likely caused by the complex interplay between pathogenic, genetic, and environmental factors, and increasing our understanding of how these relate to idiopathic PD will drive research into finding accurate diagnostic tools and disease modifying therapies.
除路易小体病理（α-突触核蛋白）外，阿尔茨海默病的特征性病变（即tau蛋白过度磷酸化和淀粉样β蛋白（Aβ）斑块）、心血管疾病以及边缘叶为主的TDP-43脑病（LATE）在帕金森病（PD）患者中常常并存。大量研究指出，tau蛋白过度磷酸化、Aβ、心血管病变和TDP-43与α-突触核蛋白之间可能存在协同关系，这可能会改变典型的病理进展模式并加速认知衰退。在此，我们讨论PD中常见伴随病变的患病率及其相互关系。此外，我们强调共同的遗传风险因素以及正在开发的生物标志物，这些标志物可能为患有并存病变的PD患者提供更高的诊断准确性。在整个PD谱系中观察到的巨大异质性很可能是由致病、遗传和环境因素之间的复杂相互作用引起的，增进我们对这些因素与特发性PD之间关系的理解将推动寻找准确诊断工具和疾病修饰疗法的研究。
