Takeda Atsushi, Baba Toru, Kikuchi Akio, Sugeno Naoto, Hasegawa Takafumi, Itoyama Yasuto, Ishioka Toshiyuki, Hirayama Kazumi, Mori Etsuro
Department of Neurology, Tohoku University, Graduate School of Medicine.
Rinsho Shinkeigaku. 2009 Nov;49(11):888-9. doi: 10.5692/clinicalneurol.49.888.
It is proposed that alpha-synucleinopathy initially affects the medulla oblongata and then progresses to more rostral brain areas ("Braak hypothesis"). According to this hypothesis, substantia nigra is affected in the later stages of PD. Another region affected in the earlier stages was reported to be olfactory bulb, although the following processes were not described in detail. On the other hand, several lines of evidence suggest that non-motor symptoms including constipation, depression, REM-sleep behavior disorder (RBD) and hyposmia may be prodromal symptoms in PD. The pathological staging postulated by the Braak hypothesis is in good agreement with the fact that these non-motor symptoms precede motor symptoms in PD, because affected brain areas in the early stages, such as dorsal vagal nucleus, locus ceruleus and olfactory bulb, are related to these non-motor features. Recently, it was reported that although half of brains corresponded to the Braak hypothesis, there were a high proportion of cases which did not fit the Braak's staging system and majority of the latter demonstrated amygdale-predominant alpha-synucleinopathy. It was also demonstrated that the Lewy pathology in olfactory bulb was closely related to the presence of alpha-synuclein pathology in amygdala. The amygdala is one of the main systems in odor perception and in PD, cortical neurons in corticomedial complex of amygdale, which have major olfactory connections, are selectively affected even in the early stages of the disease. We recently obtained the data suggesting that metabolic changes in the amygdala were associated with low scores in odor identification test. These data suggest that not only the olfactory bulb, but also the amygdala is also responsible for hyposmia in PD and that there may be another pathological process, which starts from the olfactory bulb and involves the amygdala.
有人提出，α-突触核蛋白病最初影响延髓，然后进展至更靠前的脑区（“Braak假说”）。根据这一假说，黑质在帕金森病后期受到影响。据报道，另一个在早期受影响的区域是嗅球，不过后续过程未详细描述。另一方面，有几条证据表明，包括便秘、抑郁、快速眼动睡眠行为障碍（RBD）和嗅觉减退在内的非运动症状可能是帕金森病的前驱症状。Braak假说提出的病理分期与帕金森病中这些非运动症状先于运动症状这一事实高度相符，因为早期受影响的脑区，如迷走神经背核、蓝斑和嗅球，与这些非运动特征相关。最近有报道称，虽然一半的大脑符合Braak假说，但有很大一部分病例不符合Braak分期系统，且后者大多数表现为杏仁核为主的α-突触核蛋白病。还证明了嗅球中的路易体病理与杏仁核中α-突触核蛋白病理的存在密切相关。杏仁核是嗅觉感知的主要系统之一，在帕金森病中，杏仁核皮质内侧复合体中具有主要嗅觉连接的皮质神经元即使在疾病早期也会受到选择性影响。我们最近获得的数据表明，杏仁核的代谢变化与气味识别测试中的低分有关。这些数据表明，不仅嗅球，杏仁核也与帕金森病中的嗅觉减退有关，而且可能存在另一种病理过程，该过程从嗅球开始并涉及杏仁核。
