Enduring involvement of tau, β-amyloid, α-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC)
Enduring involvement of tau, β-amyloid, α-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC)
复制标题
DOI：
10.1007/s00401-008-0439-2
复制
发表时间：
2008-12-01
影响因子：
12.7
通讯作者：
McGeer, Patrick L.
中科院分区：
文献类型：
--
作者：
Miklossy, Judith;Steele, John C.;McGeer, Patrick L.
关岛ALS/PDC是关岛特有的一种严重缠结形成疾病，其特征与阿尔茨海默病（AD）、帕金森病（PD）、进行性核上性麻痹（PSP）、ALS、皮质基底节变性（CBD）和苍白球-脑桥-黑质变性（PPND）等神经退行性疾病重叠。由于患病率正在下降，我们检查了35名临床诊断为ALS/PDC的查莫罗人患者和1946年至2006年之间尸检的两名查莫罗人对照的脑组织，以确定病理学的不同变化是否可以确定到这个时候。尽管尸检时的年龄每十年增加4.5-5岁，但我们发现tau、泛素、A β、α-突触核蛋白和TDP-43抗体在病理沉积物中没有定性差异，表明这些最近发现的蛋白质在过去60年中参与了神经发病机制。Tau和TDP-43阳性神经元，少突胶质细胞和星形胶质细胞包涵体涉及多个神经纤维束发生在ALS和PDC类型，加强了这些形式是同一疾病的一部分的概念。所获得的结果可能有助于确定关岛疾病与其他缠结形成疾病的共同性，并可能有助于监测正在发生的流行病变化。
Guam ALS/PDC is a severe tangle forming disorder endemic to Guam with features overlapping such neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease (PD), progressive supranuclear palsy (PSP), ALS, corticobasal degeneration (CBD) and pallido-ponto-nigral degeneration (PPND). Since the prevalence is declining, we examined brain tissue from 35 clinically diagnosed Chamorro patients with ALS/PDC and two Chamorro controls autopsied between 1946 and 2006, to determine if distinct variations in the pathology could be identified up to this time. Although the age at autopsy increased by 4.5-5 years per decade, we identified no qualitative differences in pathological deposits with antibodies against tau, ubiquitin, A beta, alpha-synuclein and TDP-43, indicating that these more recently identified proteins have been involved in the neuropathogenesis over the past 6 decades. Tau and TDP-43 positive neuronal, oligodendroglial and astrocytic inclusions involving multiple nerve fiber tracts occurred in both the ALS and PDC types, reinforcing the concept that these forms are part of the same disorder. The results obtained may help to define the commonality of the Guam disease with other tangle forming disorders and may help in monitoring the epidemiological changes that are taking place.