Acta Neuropathol Commun. 2014 Oct 3;2:144. doi: 10.1186/s40478-014-0144-4.
Kinesin family member 21b (kif21b) is one of the few multiple sclerosis (MS) risk genes with a presumed central nervous system function. Kif21b belongs to the kinesin family, proteins involved in intracellular transport of proteins and organelles. We hypothesised that kif21b is involved in the neurodegenerative component of MS and Alzheimer's (AD) disease. Post-mortem kinesin expression was assessed in 50 MS, 58 age and gender matched non-demented controls (NDC) and 50 AD. Kif21b expression was five-fold increased in AD compared to MS and NDC aged below 62 years (p = 8*10(-5)), three-fold between 62-72 years (p = 0.005) and not different above 72 years. No significant differences were observed between MS and NDC. In AD, kif21b expression was two-fold increased in Braak stage 6 (scoring for density of neurofibrillary tangles) compared with stage 5 (p = 0.003). In MS patients, kif21b correlated with the extent of grey matter demyelination (Spearman's rho = 0.31, p = 0.03). Abundant kif21b, defined as expression above the median, was associated with a two-fold accelerated development of the Kurtzke Expanded Disability Status Scale (EDSS) 6.0 (median time in low kif21b group 16 years vs. high kif21b 7.5 years, log-rank test p = 0.04) in MS. Given the genetic association of kif21b with MS, the results were stratified according to rs12122721[A] single nucleotide polymorphism (SNP). No association was found between kif21b expression or the time to EDSS 6 in kif21b risk SNP carriers compared to non-risk carriers. Kif21b was expressed in astrocytes in addition to neurons. Upon astrocyte activation, kif21b increased nine-fold. Abundant kif21b expression is associated with severe MS and AD pathology and with accelerated neurodegeneration independent of the kif21b risk SNP.
驱动蛋白家族成员 21b（kif21b）是少数几个多发性硬化症（MS）风险基因之一，其功能被认为与中枢神经系统有关。kif21b 属于驱动蛋白家族，该家族蛋白参与蛋白质和细胞器的细胞内运输。我们假设 kif21b 参与了多发性硬化症和阿尔茨海默病（AD）的神经退行性成分。在 50 例 MS、58 例年龄和性别匹配的非痴呆对照（NDC）和 50 例 AD 的尸检中评估了 kinesin 的表达。与 MS 和 NDC 相比，AD 中 kif21b 的表达增加了五倍（p = 8*10(-5)），在 62-72 岁之间增加了三倍（p = 0.005），而在 72 岁以上则没有差异。MS 和 NDC 之间没有观察到显著差异。在 AD 中，与 Braak 阶段 5（神经原纤维缠结密度评分）相比，kif21b 在阶段 6（p = 0.003）中的表达增加了两倍。在 MS 患者中，kif21b 与灰质脱髓鞘的程度相关（Spearman's rho = 0.31，p = 0.03）。大量 kif21b（定义为中位数以上的表达）与 Kurtzke 扩展残疾状况量表（EDSS）6.0 的两倍加速发展相关（低 kif21b 组中位数时间为 16 年，高 kif21b 组为 7.5 年，对数秩检验 p = 0.04）。鉴于 kif21b 与 MS 的遗传关联，根据 rs12122721[A]单核苷酸多态性（SNP）对结果进行了分层。与非风险携带者相比，kif21b 表达或达到 EDSS 6 的时间在 kif21b 风险 SNP 携带者中没有发现关联。kif21b 在神经元以外的星形胶质细胞中表达。星形胶质细胞激活后，kif21b 的表达增加了九倍。大量 kif21b 的表达与严重的 MS 和 AD 病理以及与 kif21b 风险 SNP 无关的神经退行性变的加速有关。
