Yoshida Mari
Institute for Medical Science of Aging, Aichi Medical University, 21 Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan.
Brain Nerve. 2009 Nov;61(11):1308-18.
Frontotemporal lobar degeneration (FTLD) has two pathological types: tau-positive and tau-negative. The most common tau-negative type is FTLD with ubiquitinated inclusions, which are composed of TAR DNA-binding protein-43 (TDP-43) (FTLD-TDP). FTLD-TDP can be subdivided into at least three main types based on the histological patterns of TDP-43-positive neuronal cytoplasmic inclusions (NCI), dystrophic neurites (DN), and neuronal intranuclear inclusions (NII). Type 1 is characterized by the predominance of long, thick DN in the cortices with numerous NCI in the hippocampus, amygdala, and basal ganglia, accompanied by the degeneration of the pyramidal tract in the spinal cord. Type 2 is characterized by numerous NCI in the cortices, associated with the involvement of lower motor neurons. TDP-43-positive skein-like inclusions and round inclusions identical to those observed in amyotrophic lateral sclerosis (ALS) patients are also seen in the lower motor neurons in type 2. Type 3 is characterized by both NCI and DN with variable NII. Lower motor neuron involvement is usually less prominent in types 1 and 3 than in type 2. These findings suggest that FTLD-TDP and ALS are at two ends of the same disease spectrum, i. e., TDP-43 proteinopathy.
额颞叶变性（FTLD）有两种病理类型：tau蛋白阳性和tau蛋白阴性。最常见的tau蛋白阴性类型是伴有泛素化包涵体的FTLD，其由TAR DNA结合蛋白43（TDP - 43）组成（FTLD - TDP）。基于TDP - 43阳性神经元胞质包涵体（NCI）、营养不良性神经突（DN）和神经元核内包涵体（NII）的组织学模式，FTLD - TDP可至少细分为三种主要类型。1型的特征是皮质中长而粗的DN占优势，海马、杏仁核和基底神经节中有大量NCI，伴有脊髓锥体束变性。2型的特征是皮质中有大量NCI，伴有下运动神经元受累。在2型的下运动神经元中也可见到与肌萎缩侧索硬化（ALS）患者中观察到的TDP - 43阳性丝状包涵体和圆形包涵体相同的结构。3型的特征是既有NCI又有DN，伴有不同程度的NII。1型和3型中下运动神经元受累通常不如2型明显。这些发现表明，FTLD - TDP和ALS处于同一疾病谱的两端，即TDP - 43蛋白病。
