Head Elizabeth, Lott I T, Cribbs David H, Cotman Carl W, Rohn Troy T
Institute for Brain Aging and Dementia, University of California at Irvine, Irvine, CA 92697-4540, USA.
Neurosci Lett. 2002 Sep 13;330(1):99-103. doi: 10.1016/s0304-3940(02)00705-x.
Individuals with Down syndrome (DS) and Alzheimer's disease (AD) develop senile plaques, neurofibrillary tangles (NFT), and neuron loss. Recent studies demonstrate the activation of apoptotic pathways in AD; less data is available in DS. The DS brain was examined using immunocytochemistry and antibodies against the active fragment of caspase-8 (AC, 8) and to caspase-3 cleavage products of fodrin (CCP), a neuronal cytoskeleton protein. The hippocampus demonstrated widespread accumulation of fodrin CCP and AC8 in NFTs and dystrophic neurites. Individual neurons contained intracellular beta-amyloid (Abeta) and fodrin CCP providing evidence that caspase activation can occur with both NFT and Abeta. Abeta within or around neurons in addition to contributing to NFT formation may also trigger apoptotic pathways. Caspase activation may lead to the cleavage of critical cellular proteins and neuronal cell death associated with DS.
患有唐氏综合征（DS）和阿尔茨海默病（AD）的个体都会出现老年斑、神经原纤维缠结（NFT）以及神经元丢失。近期研究表明AD中存在凋亡途径的激活；而关于DS的此类数据较少。使用免疫细胞化学方法以及针对半胱天冬酶 - 8（AC，8）的活性片段和针对神经元细胞骨架蛋白血影蛋白的半胱天冬酶 - 3切割产物（CCP）的抗体对DS大脑进行了检测。海马体显示出血影蛋白CCP和AC8在NFTs及营养不良性神经突中广泛积聚。单个神经元含有细胞内β - 淀粉样蛋白（Aβ）和血影蛋白CCP，这表明半胱天冬酶激活可同时发生于NFT和Aβ情况中。神经元内或其周围的Aβ除了有助于NFT形成外，还可能触发凋亡途径。半胱天冬酶激活可能导致关键细胞蛋白的切割以及与DS相关的神经元细胞死亡。
