ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, United States.
Neurodegenerative Diseases Research Unit, Biogen, Boston, MA, United States.
Handb Clin Neurol. 2023;192:57-71. doi: 10.1016/B978-0-323-85538-9.00012-2.
Parkinson's disease is a progressive neurodegenerative disorder that is associated with motor and nonmotor symptoms. Accumulation of misfolded α-synuclein is considered a key pathological feature during disease initiation and progression. While clearly deemed a synucleinopathy, the development of amyloid-β plaques, tau-containing neurofibrillary tangles, and even TDP-43 protein inclusions occur within the nigrostriatal system and in other brain regions. In addition, inflammatory responses, manifested by glial reactivity, T-cell infiltration, and increased expression of inflammatory cytokines, plus other toxic mediators derived from activated glial cells, are currently recognized as prominent drivers of Parkinson's disease pathology. However, copathologies have increasingly been recognized as the rule (>90%) and not the exception, with Parkinson's disease cases on average exhibiting three different copathologies. While microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy may have an impact on disease progression, α-synuclein, amyloid-β, and TDP-43 pathology do not seem to contribute to progression.
帕金森病是一种进行性神经退行性疾病，与运动和非运动症状有关。在疾病的起始和进展过程中，错误折叠的α-突触核蛋白的积累被认为是一个关键的病理特征。虽然明确被认为是一种突触核蛋白病，但淀粉样β斑块、含有tau 的神经原纤维缠结以及甚至 TDP-43 蛋白包含体在黑质纹状体系统和其他脑区中发生。此外，炎症反应，表现为神经胶质反应、T 细胞浸润和炎症细胞因子表达增加，加上来自激活的神经胶质细胞的其他毒性介质，目前被认为是帕金森病病理学的主要驱动因素。然而，共病已越来越被认为是常态（>90%）而不是例外，帕金森病病例平均表现出三种不同的共病。虽然微梗死、动脉粥样硬化、小动脉硬化和脑淀粉样血管病可能对疾病进展有影响，但α-突触核蛋白、淀粉样β 和 TDP-43 病理学似乎不会导致进展。
