Krabbe's disease (KD) is primarily a demyelinating disorder, but recent studies have identified the presence of neuronal protein aggregates in the brain, at least partially composed by alpha-synuclein (α-syn). The role of this protein aggregation in the pathogenesis of KD is largely unknown, but it has added KD to a growing list of lysosomal storage diseases that can be also be considered as proteinopathies. While the presence of these protein aggregates within the KD brain is now appreciated, the remainder of the central nervous system (CNS) remains uncharacterized. This study is the first to report the presence of thioflavin-S reactive inclusions throughout the spinal cord of both murine and human spinal tissue. Stereological analysis revealed the temporal and spatial accumulation of these inclusions within the neurons of the ventral spinal cord vs. those located in the dorsal cord. This study also confirmed that these thio-S positive accumulations are present within neuronal populations and are made up at least in part by α-syn in both the twitcher mouse and cord autopsied material from affected human patients. Significantly, neonatal gene therapy for galactosylceramidase, a treatment that strongly improves the survival and health of KD mice, but not bone marrow transplantation prevents the formation of these inclusions in spinal neurons. These results expand the understanding of α-syn protein aggregation within the CNS of individuals afflicted with KD and underlines the tractability of this problem via early gene therapy, with potential impact to other synucleinopathies such as PD.

克拉伯氏病（Krabbe's disease，KD）主要是一种脱髓鞘疾病，但最近的研究已经确定了大脑中神经元蛋白质聚集体的存在，至少部分由α-突触核蛋白（α-syn）组成。这种蛋白聚集在KD发病机理中的作用在很大程度上尚不清楚，但它已将KD添加到了越来越多的溶酶体贮积病中，这些病也被认为是蛋白病。现在人们已经认识到这些蛋白质聚集体在KD大脑中的存在，但其余中枢神经系统（CNS）仍未鉴定。这项研究是第一个报告在鼠和人脊髓组织的整个脊髓中都存在硫代黄素-S反应性内含物的研究。体视学分析显示，腹侧脊髓神经元与背侧脊髓神经元相比，这些夹杂物在时间和空间上均有积累。这项研究还证实，这些硫代S阳性积聚存在于神经元群体中，并且至少部分由受感染人类患者的抽搐小鼠和脐带尸检材料中的α-syn组成。重要的是，用于半乳糖基神经酰胺酶的新生儿基因疗法可以大大改善KD小鼠的生存和健康，但不能通过骨髓移植来阻止其在脊髓神经元中的形成。这些结果扩大了对患KD的个体中枢神经系统中α-syn蛋白聚集的理解，并强调了通过早期基因治疗可解决该问题的方法，