Albrecht Steffen, Bogdanovic Nenad, Ghetti Bernardino, Winblad Bengt, LeBlanc Andréa C
Department of Pathology, McGill University, Montréal Children's Hospital, Montréal, Quebec, Canada.
J Neuropathol Exp Neurol. 2009 Dec;68(12):1282-93. doi: 10.1097/NEN.0b013e3181c1da10.
We previously demonstrated the activation of caspase-6 (Casp-6) in the hippocampus and cortex in cases of mild, moderate, severe, and very severe Alzheimer disease (AD). To determine whether Casp-6 is also activated in familial AD, we performed an immunohistochemical analysis of active Casp-6 and Tau cleaved by Casp-6 in temporal cortex and hippocampal tissue sections from cases of familial AD. The cases included 5 carrying the amyloid precursor protein K670N and M671L Swedish mutation, 1 carrying the amyloid precursor protein E693G Arctic mutation, 2 each carrying the Presenilin I M146V, F105L, A431E, V261F, and Y115C mutations, and 1 with the Presenilin II N141I mutation. Active Casp-6 immunoreactivity was found in all cases. Caspase-6 immunoreactivity was observed in neuritic plaques or in some cases cotton-wool plaques, and in neuropil threads and neurofibrillary tangles. These results indicate that Casp-6 is activated in familial forms of AD, as previously observed in sporadic forms. Because sporadic and familial AD cases have similar pathological features, these results support a fundamental role of Casp-6 in the pathophysiology of both familial and sporadic AD.
我们之前已证明，在轻度、中度、重度和极重度阿尔茨海默病（AD）病例中，海马体和皮质中的半胱天冬酶-6（Casp-6）被激活。为了确定Casp-6在家族性AD中是否也被激活，我们对家族性AD病例颞叶皮质和海马组织切片中活性Casp-6及被Casp-6切割的Tau进行了免疫组织化学分析。这些病例包括5例携带淀粉样前体蛋白K670N和M671L瑞典突变者、1例携带淀粉样前体蛋白E693G北极突变者、2例分别携带早老素I M146V、F105L、A431E、V261F和Y115C突变者，以及1例携带早老素II N141I突变者。在所有病例中均发现了活性Casp-6免疫反应性。在神经炎性斑块中或在某些病例的棉絮状斑块中、神经毡丝和神经原纤维缠结中观察到了Casp-6免疫反应性。这些结果表明，Casp-6在家族性AD形式中被激活，正如之前在散发性形式中所观察到的那样。由于散发性和家族性AD病例具有相似的病理特征，这些结果支持Casp-6在家族性和散发性AD的病理生理学中起基本作用。
