Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia.
Ann N Y Acad Sci. 2010 Jan;1184:188-95. doi: 10.1111/j.1749-6632.2009.05118.x.
To identify the progression of pathology over the entire course of Parkinson's disease, we longitudinally followed a clinical cohort to autopsy and identified three clinicopathological phenotypes that progress at different rates. Typical Parkinson's disease has an initial rapid loss of midbrain dopamine neurons with a slow progression of Lewy body infiltration into the brain (over decades). Dementia intervenes late when Lewy bodies invade the neocortex. Older onset patients (> 70 years old) dement earlier and have much shorter disease durations. Paradoxically, they have far more alpha-synuclein-containing Lewy bodies throughout the brain, and many also have additional age-related plaque pathology. In contrast, dementia with Lewy bodies has the shortest disease course, with substantive amounts of Lewy bodies and Alzheimer-type pathologies infiltrating the brain. These data suggest that two age-related factors influence pathological progression in Parkinson's disease--the age at symptom onset and the degree and type of age-related Alzheimer-type pathology.
为了确定帕金森病整个病程中的病理学进展，我们对一个临床队列进行了纵向随访至尸检，并确定了三种以不同速度进展的临床病理表型。典型的帕金森病具有中脑多巴胺神经元的初始快速丧失，以及路易体逐渐渗透到大脑的缓慢进展（数十年）。当路易体侵入新皮质时，痴呆症会介入晚期。发病年龄较大（> 70 岁）的患者会更早痴呆，且疾病持续时间更短。矛盾的是，他们的大脑中含有更多的α-突触核蛋白的路易体，并且许多人还具有其他与年龄相关的斑块病理学。相比之下，路易体痴呆症的疾病过程最短，大量的路易体和阿尔茨海默病型病理学渗透到大脑中。这些数据表明，两个与年龄相关的因素影响帕金森病的病理学进展——症状发作的年龄以及与年龄相关的阿尔茨海默病型病理学的程度和类型。
