Su J H, Deng G, Cotman C W
Institute for Brain Aging and Dementia, University of California, Irvine 92697-4540, USA.
J Neuropathol Exp Neurol. 1997 Jan;56(1):86-93. doi: 10.1097/00005072-199701000-00009.
We have shown that many neurons in Alzheimer's disease (AD) exhibit terminal deoxynucleotidyl transferase (TdT) labeling for DNA strand breaks, and upregulation of Bcl-2 is associated with neurons exhibiting nuclear DNA fragmentation, while downregulation of Bcl-2 is associated with tangle-bearing neurons in AD brains. Consequently, we examined the expression of bcl-associated X (Bax) protein in AD brain. Immunoreactivity for Bax was seen in neurons and microglia of the hippocampal formation, and was elevated in the majority of AD cases as compared to control cases. Interestingly, 3 transitional cases, which had mild degeneration changes, exhibited relatively high levels of Bax immunoreactivity. Most Bax-positive neurons showed either TdT-labeled nuclei or Bcl-2 immunoreactivity. Although Bax immunoreactivity was detected within most early tangle-bearing neurons, many Bax-positive neurons did not colocalize with later-stage tangle-bearing neurons. In regions containing relatively few tangles in mild AD brains, many TdT-labeled neurons were immunolabeled with Bax antibody and most of them lacked evidence of neurofibrillary changes. These findings suggest that Bax may contribute to neuronal cell death in AD. Furthermore, DNA damage and the upregulation of Bax appear to precede tangle formation or may represent an alternative pathway of cell death in AD.
我们已经表明，阿尔茨海默病（AD）中的许多神经元表现出针对DNA链断裂的末端脱氧核苷酸转移酶（TdT）标记，并且Bcl-2的上调与表现出核DNA片段化的神经元相关，而Bcl-2的下调与AD脑中有神经缠结的神经元相关。因此，我们检测了AD脑中bcl相关X蛋白（Bax）的表达。在海马结构的神经元和小胶质细胞中可见Bax的免疫反应性，并且与对照病例相比，大多数AD病例中的Bax免疫反应性升高。有趣的是，3例有轻度变性改变的过渡病例表现出相对较高水平的Bax免疫反应性。大多数Bax阳性神经元显示出TdT标记的细胞核或Bcl-2免疫反应性。虽然在大多数早期有神经缠结的神经元中检测到Bax免疫反应性，但许多Bax阳性神经元并不与后期有神经缠结的神经元共定位。在轻度AD脑中缠结相对较少的区域，许多TdT标记的神经元被Bax抗体免疫标记，并且它们中的大多数缺乏神经原纤维变化的证据。这些发现表明，Bax可能在AD的神经元细胞死亡中起作用。此外，DNA损伤和Bax的上调似乎先于缠结形成，或者可能代表AD中细胞死亡的另一种途径。
