Saito Yuko, Ruberu Nyoka N, Sawabe Motoji, Arai Tomio, Kazama Hirohito, Hosoi Takayuki, Yamanouchi Hiroshi, Murayama Shigeo
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
J Neuropathol Exp Neurol. 2004 Jul;63(7):742-9. doi: 10.1093/jnen/63.7.742.
To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging, we investigated the incidence of LBs in 1,241 consecutive autopsy cases (663 males and 578 females). LB pathology was identified histologically in sections stained with hematoxylin and eosin and with anti-ubiquitin and anti-alpha-synuclein antibodies. Cases without LBs were classified as LB stage 0 (987 cases). Cases with LBs were classified as follows: LB stage I = incidental LBs (149 cases); LB stage II = LB-related degeneration without attributable clinical symptoms (47 cases); LB stage III = Parkinson disease without dementia (10 cases); LB stage IV = dementia with Lewy bodies (DLB) transitional (limbic) form (25 cases); and LB stage V = DLB neocortical form (23 cases). The average age at death was greater for those cases with LBs. There were no gender differences in the LB pathology. G842A polymorphism in the paraoxonase I gene was associated with men in LB stage II or above and suggests a gender-specific risk factor. LB stage V had higher stages of neurofibrillary tangle and senile plaque involvement and also had a higher frequency of apolipoprotein E epsilon4. Our findings indicate that LBs are associated with cognitive decline, either independently or synergistically with neurofibrillary tangles and senile plaques.
为阐明路易小体（LB）相关的α-突触核蛋白病在衰老过程中的意义，我们调查了1241例连续尸检病例（663例男性和578例女性）中路易小体的发生率。通过苏木精和伊红染色以及抗泛素和抗α-突触核蛋白抗体染色的切片进行组织学鉴定LB病理学。无路易小体的病例分类为LB 0期（987例）。有路易小体的病例分类如下：LB I期=偶发性路易小体（149例）；LB II期=与路易小体相关的变性但无相关临床症状（47例）；LB III期=无痴呆的帕金森病（10例）；LB IV期=路易体痴呆（DLB）过渡（边缘）型（25例）；LB V期=DLB新皮质型（23例）。有路易小体的病例死亡时的平均年龄更大。路易小体病理学无性别差异。对氧磷酶I基因中的G842A多态性与II期及以上的男性相关，提示存在性别特异性危险因素。LB V期神经原纤维缠结和老年斑累及程度更高，载脂蛋白E ε4的频率也更高。我们的研究结果表明，路易小体与认知功能下降相关，可能独立起作用，也可能与神经原纤维缠结和老年斑协同起作用。
