Lippa Carol F, Rosso Andrea L, Stutzbach Lauren D, Neumann Manuela, Lee Virginia M-Y, Trojanowski John Q
Drexel University College of Medicine Philadelphia, Philadelphia, Pennsylvania 19102, USA.
Arch Neurol. 2009 Dec;66(12):1483-8. doi: 10.1001/archneurol.2009.277.
To assess the transactive response DNA-binding protein 43 (TDP-43) burden in familial forms of Alzheimer disease (FAD) and Down syndrome (DS) to determine whether TDP-43 inclusions are also present.
Using standard immunohistochemical techniques, we examined brain tissue samples from 42 subjects with FAD and 14 with DS.
We found pathological TDP-43 aggregates in 14.0% of participants (6 of 42 and 2 of 14 participants with FAD and DS, respectively). In both FAD and DS, TDP-43 immunoreactivity did not colocalize with neurofibrillary tangles. Occasionally participants with FAD or DS had TDP-43-positive neuropil threads or dots. Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions. A similar distribution of TDP-43 inclusions is seen in sporadic Alzheimer disease, but it differs from that seen in amyotrophic lateral sclerosis and frontotemporal dementia.
Transactive response DNA-binding protein 43 pathology occurs in FAD and DS, similar to that observed in sporadic Alzheimer disease. Thus, pathological TDP-43 may contribute the cognitive impairments in familial and sporadic forms of Alzheimer disease.
评估家族性阿尔茨海默病（FAD）和唐氏综合征（DS）中反式激活应答DNA结合蛋白43（TDP-43）的负荷，以确定是否也存在TDP-43包涵体。
我们使用标准免疫组织化学技术，检查了42例FAD患者和14例DS患者的脑组织样本。
我们在14.0%的参与者中发现了病理性TDP-43聚集体（FAD患者中有6例，DS患者中有2例）。在FAD和DS中，TDP-43免疫反应性均未与神经原纤维缠结共定位。偶尔，FAD或DS患者会出现TDP-43阳性的神经毡丝或点状结构。总体而言，杏仁核最常受累，其次是海马体，新皮质区域未发现TDP-43病理改变。散发性阿尔茨海默病中也可见类似的TDP-43包涵体分布，但与肌萎缩侧索硬化症和额颞叶痴呆中的分布不同。
FAD和DS中存在反式激活应答DNA结合蛋白43病理改变，与散发性阿尔茨海默病中观察到的情况相似。因此，病理性TDP-43可能导致家族性和散发性阿尔茨海默病的认知障碍。
