Department of Neurology, the Affiliated Huaian First People's Hospital of Nanjing Medical University, Jiangsu, China.
Division of Neuropathology, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.
J Alzheimers Dis. 2021;81(1):201-207. doi: 10.3233/JAD-210114.
Parkinson's disease (PD) and Alzheimer's disease (AD) are the two most prevalent neurodegenerative diseases associated with age. Pathological studies have shown that these two diseases share a certain degree of neuropathological overlap. AD neuropathologic change contributes to cognitive impairment in PD. However, the impact of AD pathology on other clinical phenotypes in PD remains largely unknown.
Herein we aimed to assess the impact of co-occurring AD neuropathologic change on the clinical phenotypes of PD.
We examined 46 autopsy brains of PD patients and available clinical information to retrospectively assess the effects of comorbid AD pathology on dementia, hallucinations, and dyskinesia commonly seen in advanced PD.
AD neuropathology significantly increased the risk of hallucinations and dementia, but not dyskinesia in PD patients. Surprisingly, diffuse Lewy body pathology, but not AD pathology, was associated with the occurrence of dementia and hallucinations. Most importantly, we reported that the severity of neuronal loss in the locus coeruleus (LC), but not the severity of neuronal loss in the substantia nigra (SN), was associated with the occurrence of dyskinesia in advanced PD patients, while neither Lewy body scores in SN nor LC had significant effects.
We show for the first time that neuronal loss in LC contributes to dyskinesia. Understanding the relationships between the two distinct pathologies and their relevant clinical phenotypes will be crucial in the development of effective disease-modifying therapies for PD.
帕金森病（PD）和阿尔茨海默病（AD）是与年龄相关的两种最常见的神经退行性疾病。病理学研究表明，这两种疾病具有一定程度的神经病理学重叠。AD 神经病理学改变导致 PD 患者认知障碍。然而，AD 病理学对 PD 其他临床表型的影响在很大程度上仍不清楚。
本研究旨在评估 AD 神经病理学改变共存对 PD 临床表型的影响。
我们检查了 46 例 PD 患者的尸检脑和可获得的临床信息，以回顾性评估共患 AD 病理学对 PD 患者常见的痴呆、幻觉和运动障碍的影响。
AD 病理学显著增加了 PD 患者发生幻觉和痴呆的风险，但不增加运动障碍的风险。令人惊讶的是，弥漫性路易体病，而不是 AD 病理学，与痴呆和幻觉的发生有关。最重要的是，我们报告说蓝斑（LC）神经元丢失的严重程度与晚期 PD 患者运动障碍的发生有关，而黑质（SN）神经元丢失的严重程度与运动障碍的发生无关。虽然 SN 中的路易体评分和 LC 都没有显著影响。
我们首次表明 LC 中的神经元丢失与运动障碍有关。了解这两种不同病理及其相关临床表型之间的关系对于开发有效的 PD 疾病修饰治疗方法至关重要。
