NGF-RESPONSIVENESS AND AMYLOID GENE EXPRESSION IN ALZHEIMER'S DISEASE

该项目解决了NGF赤字是否- 反应性可能会低估某些神经病理变化 发生在阿尔茨海默病(AD)的基底前脑。我们建议 检验神经生长因子(NGF-R)表达的假设 基因是基底细胞形态完整性的敏感指标 前脑胆碱能神经元(Ch1-Ch4细胞组)，增加 NGF-R mRNA水平与高水平神经元肥大相关 皮质靶区NGF表达减少，NGF-R和NGF-R水平降低 神经元萎缩与生长因子剥夺相关。就地 NGF-R mRNA杂交将与定量检测相结合 细胞数量和细胞杂交强度以记录变化 NGF-R基因在AD患者CH1-CH4细胞组成分中的表达。 皮质靶点可能发生淀粉样蛋白沉积的一种机制 区域是由淀粉样蛋白前体表达的变化引起的 (APP)基因在基底节区皮质投射胆碱能神经元内 前脑。因此，我们将测试这样的假设，即特定形式的APP MRNA转录本可能优先与NGF-1表达降低相关 阿尔茨海默病的反应性。这些实验将结合在一起 新开发的逆转录酶原位杂交方法- 聚合酶链式反应(R-PCR)提供相对定量 阿尔茨海默病患者APP基因表达的变化。

This project addresses the question of whether deficits in NGF- responsiveness may underly some of the neuropathological changes which occur in the basal forebrain in Alzheimer's disease (AD). We propose to test the hypothesis that expression of the nerve growth factor (NGF-R) gene is a sensitive indicator of the morphological integrity of basal forebrain cholinergic neurons (Ch1 - Ch4) cell groups), with increased levels of NGF-R mRNA and neuronal hypertrophy correlated with high levels of NGF in cortical target regions, and decrease levels of NGF-R and neuronal atrophy correlated with growth factor deprivation. In situ hybridization of NGF-R mRNA will be combined with quantitative measures of cell number and cellular hybridization intensity to document changes in NGF-R gene expression within components of the Ch1-Ch4 cell groups in AD. One mechanism by which amyloid deposition may occur with cortical target regions is by changes in the expression of the amyloid protein precursor (APP) gene within cortically-projecting cholinergic neurons of the basal forebrain. Thus, we will test the hypothesis that a specific form of APP mRNA transcript may be preferentially correlated with decreased NGF- responsiveness in Alzheimer's disease. These experiments will combine in situ hybridization methods with recently developed reverse transcriptase- polymerase chain reaction (R-PCR) to provide relative quantification of changes in the ratios of APP mRNA in AD.