Gap-43 message levels in anterior cerebellum in Alzheimer's disease
Gap-43 message levels in anterior cerebellum in Alzheimer's disease
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DOI：
10.1016/0169-328x(95)00257-s
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Coleman, PD
中科院分区：
文献类型：
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作者：
Cheetham, JE;Martzen, MR;Coleman, PD
我们之前报道过阿尔茨海默病（AD）患者额叶联合皮层（9区）中生长相关蛋白（GAP-43）信息的减少与含有神经原纤维缠结（nft）[9]的神经元密度增加有关。这一发现导致AD中GAP-43信息的减少可能与nft有关，而不是AD病理的其他方面。因此，我们预测，在AD患者未受nft影响的大脑区域，GAP-43的信息水平应该与对照组相似。小脑已知有许多AD的病理，包括弥漫性斑块（DPs）、小胶质细胞活化和反应性星形胶质细胞。然而，nft在小脑中并不常见。从AD和对照组的前小脑中提取mRNA，进行Northern和slot印迹，并与GAP-43探针杂交。用聚（dT）和葡萄糖-3-磷酸脱氢酶探针进行归一化。AD病例的平均相对GAP-43消息水平为0.582，对照病例为0.448。这23%的差异没有达到统计学意义。AD组内回归分析显示，小脑皮层GAP-43信息水平与小脑皮层弥漫性斑块密度无显著相关。小脑皮层的GAP-43信息水平也与神经斑块的总密度或皮质区nft的总密度无关，后者被用作疾病严重程度的指标。本文报道的数据还强调，先前报道的阿尔茨海默病[9]额叶关联皮层中GAP-43 mRNA水平的（nft依赖性）降低似乎是区域特异性的，而不是普遍的大脑现象。AD患者小脑中保持正常的GAP-43信息水平，与NFT形成相关的事件对阿尔茨海默病中GAP-43的表达有重要影响的假设是一致的。
We have previously reported that decreased growth-associated protein (GAP-43) message in frontal association cortex (area 9) of Alzheimer's disease (AD) patients is associated with increased density of neurons containing neurofibrillary tangles (NFTs) [9]. This finding leads to the hypothesis that decreased GAP-43 message in AD may be related to NFTs, rather than to some other aspect of AD pathology. Therefore, we predicted that in areas of brain unaffected by NFTs in AD the GAP-43 message levels should be similar to those of controls. The cerebellum is known to have a number of pathologies of AD, including diffuse plaques (DPs), microglial activation and reactive astrocytes. NFTs, however, are not typically found in the cerebellum. mRNA was extracted from anterior cerebellum of AD and control cases, Northern- and slot-blotted and hybridized against a GAP-43 probe. Poly(dT) and glucose-3-phosphate dehydrogenase probes were used for normalization. The average relative GAP-43 message level was 0.582 in the AD cases and 0.448 in control cases. This 23% difference failed to reach statistical significance. Regression analysis within the AD group demonstrated that GAP-43 message level in cerebellar cortex was not significantly correlated with diffuse plaque density in cerebellar cortex. GAP-43 message levels in cerebellar cortex were also not correlated with summed density of neuritic plaques or summed density of NFTs in cortical regions - here used as an index of severity of disease. The data reported here also emphasize that the (NFT-dependent) reduction in GAP-43 mRNA levels previously reported in frontal association cortex in Alzheimer's disease [9] appears to be region specific and not a general brain phenomenon. The preservation of normal GAP-43 message levels in the cerebellum in AD is consistent with the hypothesis that events related to NFT formation have a major impact on the expression of GAP-43 in Alzheimer's disease.