Wright C I, Geula C, Mesulam M M
Bullard and Denny-Brown Laboratories, Department of Neurology, Beth Israel Hospital, Boston, MA 02215.
Ann Neurol. 1993 Sep;34(3):373-84. doi: 10.1002/ana.410340312.
Butyrylcholinesterase (BChE) and an altered form of acetylcholinesterase (AChE) accumulate in the plaques and tangles of Alzheimer's disease (AD). The sources for these plaque- and tangle-bound cholinesterases have not been identified. We now report that AChE and BChE activities with pH preferences and inhibitor selectivities identical to those of plaque- and tangle-bound cholinesterases are found in the astrocytes and oligodendrocytes of control and AD brains. These glial-type cholinesterases are selectively inhibited by indolamines and protease inhibitors. In control brains glial-type cholinesterases appear confined to the intracellular space, whereas in patients with AD they decorate plaques and tangles as well. In control and AD brains AChE-positive glia are distributed throughout the cortical layers and subcortical white matter, whereas BChE-positive glia reach high densities only in the deep cortical layers and white matter. In non-AD control brains, the ratio of BChE to AChE glia was higher in entorhinal and inferotemporal cortex, two regions with a high susceptibility to the pathology of AD, than in primary somatosensory and visual cortex, two areas with a relatively lower susceptibility to the disease process. There was no age-related differences in the density or distribution of cholinesterase-positive glia. In comparison with age-matched control specimens, AD brains had a significantly higher density of BChE glia and a lower density of AChE glia in entorhinal and inferotemporal regions but not in the primary somatosensory or visual areas. These results suggest that glia constitute a likely source for the cholinesterase activity of plaques and tangles and that a high ratio of BChE- to AChE-positive glia may play a permissive or causative role in the neuropathology of AD.
丁酰胆碱酯酶（BChE）和一种改变形式的乙酰胆碱酯酶（AChE）在阿尔茨海默病（AD）的斑块和缠结中积聚。这些与斑块和缠结结合的胆碱酯酶的来源尚未确定。我们现在报告，在对照和AD脑的星形胶质细胞和少突胶质细胞中发现了具有与斑块和缠结结合的胆碱酯酶相同的pH偏好和抑制剂选择性的AChE和BChE活性。这些胶质细胞型胆碱酯酶被吲哚胺和蛋白酶抑制剂选择性抑制。在对照脑中，胶质细胞型胆碱酯酶似乎局限于细胞内空间，而在AD患者中，它们也会修饰斑块和缠结。在对照和AD脑中，AChE阳性胶质细胞分布于整个皮质层和皮质下白质，而BChE阳性胶质细胞仅在皮质深层和白质中达到高密度。在非AD对照脑中，内嗅皮质和颞下皮质这两个对AD病理高度敏感的区域中，BChE阳性胶质细胞与AChE阳性胶质细胞的比例高于初级体感皮质和视觉皮质这两个对疾病进程相对不敏感的区域。胆碱酯酶阳性胶质细胞的密度或分布没有年龄相关差异。与年龄匹配的对照标本相比，AD脑在内嗅和颞下区域的BChE阳性胶质细胞密度显著更高，而AChE阳性胶质细胞密度更低，但在初级体感或视觉区域并非如此。这些结果表明，胶质细胞可能是斑块和缠结中胆碱酯酶活性的来源，并且BChE阳性胶质细胞与AChE阳性胶质细胞的高比例可能在AD的神经病理学中起促进或致病作用。
