神经退行性疾病,如帕金森病(PD),阿尔茨海默病(AD),和肌萎缩侧索硬化症(ALS)传统上被严格认为是神经系统疾病。然而,临床表现不仅限于神经系统,和非中枢神经系统(CNS)表现,尤其是胃肠道(GI)症状,很常见。我们的目标是了解存档的非中枢神经系统组织中病理的全身分布,作为ALS患者生活中常规临床实践的一部分。我们检查了继续发展为ALS的13人的组织;包括散发性ALS(n=12)和C9orf72六核苷酸重复扩增(n=1)。组织队列由来自21例手术病例的68例福尔马林固定石蜡包埋样本组成(一些患者在其一生中有超过一例病例),来自8个器官系统,我们检查了磷酸化TDP-43(pTDP-43)病理的证据。我们在胃肠道的多种细胞类型中鉴定了pTDP-43聚集体,包括固有层内的巨噬细胞和树突状细胞;以及肌间神经丛的神经节/神经元和神经胶质细胞。淋巴结实质内也注意到聚集体,血管内皮细胞,和软骨细胞.我们注意到,在所有非CNSpTDP-43病理的病例中,在ALS诊断之前存在聚集物,在某些情况下,聚集物出现在神经系统症状发作之前超过10年.这些数据表明,具有显微镜无法解释的非CNS症状的患者可能具有隐匿性蛋白质聚集,可以在神经系统受累之前很多年检测到。
Neurodegenerative diseases such as Parkinson\'s disease (PD), Alzheimer\'s disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non-central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of pathology in archived non-CNS tissues, taken as part of routine clinical practice during life from people with ALS. We examined tissue from 13 people who went on to develop ALS; including sporadic ALS (n = 12) and C9orf72 hexanucleotide repeat expansion (n = 1). The tissue cohort consisted of 68 formalin-fixed paraffin embedded samples from 21 surgical cases (some patients having more than one
case over their lifetimes), from 8 organ systems, which we examined for evidence of phosphorylated TDP-43 (pTDP-43) pathology. We identified pTDP-43 aggregates in multiple cell types of the GI tract, including macrophages and dendritic cells within the lamina propria; as well as ganglion/neuronal and glial cells of the myenteric plexus. Aggregates were also noted within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non-CNS pTDP-43 pathology, aggregates were present prior to ALS diagnosis and in some instances preceded neurological symptom onset by more than 10 years. These data imply that patients with microscopically unexplained non-CNS symptoms could have occult protein aggregation that could be detected many years prior to neurological involvement.