Alzheimer disease pathology in amyotrophic lateral sclerosis
Alzheimer disease pathology in amyotrophic lateral sclerosis
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DOI：
10.1007/s00401-004-0843-1
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发表时间：
2004-06-01
影响因子：
12.7
通讯作者：
Bowser, R
中科院分区：
文献类型：
--
作者：
Hamilton, RL;Bowser, R
肌萎缩侧索硬化症(ALS)的特征是上下运动神经元的变性。在一些ALS患者中，可能存在痴呆或失语(ALS-D)。痴呆症最常见的是额颞叶痴呆(FTD)，其中许多病例在齿状回神经元以及额叶和颞叶的浅层中有泛素阳性、tau阴性的包涵体。在表现为FTD的病例中发现了相同的包涵体，并被指定为运动神经元病(MND)包涵体。据报道，无MND包涵体的ALS-D病例表现为新皮质胶质细胞增厚、神经元丢失和浅表海绵样变，但也有零星的ALS合并阿尔茨海默病(AD)病例报道。为了确定AD病理是否在ALS的痴呆或失语综合征中起作用，我们回顾了匹兹堡大学医学中心诊断的30例散发性ALS。24.1%的病例有ALS-D的临床病史，其中57%有MND包涵体。尽管伴有MND包涵体的ALS-D患者通常有淀粉样β蛋白(Abeta)斑块，但没有神经性斑块。3例ALS-D无MND包涵体，其中2例符合AD的病理标准。1例ALS-D患者表现为严重的淀粉样血管病变，但未见神经炎斑块或MND包涵体。在没有痴呆的ALS患者中没有发现MND包涵体；然而，4名没有痴呆或失语的患者显示中度或频繁数量的神经炎斑块。总之，我们发现，大约30%的ALS痴呆症患者患有AD，一些没有明显痴呆的ALS患者有显著的AD病理改变。
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. In some ALS patients, dementia or aphasia may be present (ALS-D). The dementia is most commonly a frontotemporal dementia (FTD), and many of these cases have ubiquitin-positive, tau-negative inclusions in neurons of the dentate gyrus and superficial layers of the frontal and temporal lobes. Identical inclusions have been found in cases presenting with FTD and have been designated motor neuron disease (MND)-inclusions. Cases of ALS-D without MND-inclusions have been reported to show neocortical gliosis, neuronal loss, and superficial spongiosis, but there have also been scattered case reports of ALS with Alzheimer's disease (AD). To determine whether AD pathology may play a role in the dementia or aphasia syndromes in ALS, we reviewed 30 cases of sporadic ALS diagnosed at the University of Pittsburgh Medical Center. A clinical history of ALS-D was found in 24.1% of the cases, of which 57% had MND-inclusions. Although the ALS-D cases with MND-inclusions typically had amyloid-beta (Abeta) plaques, there were no neuritic plaques. Three cases of ALS-D had no MND-inclusions, and two of these fulfilled pathological criteria for AD. One ALS-D case showed severe amyloid angiopathy but no neuritic plaques or MND-inclusions. MND-inclusions were not found in any ALS case without dementia; however, four patients without dementia or aphasia showed moderate or frequent numbers of neuritic plaques. In conclusion, we found that approximately 30% of ALS cases with dementia have AD and that some ALS cases without frank dementia have significant AD pathology.