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

阿尔茨海默病中的 NGF 反应性和淀粉样蛋白基因表达

• 批准号: 6098259
• 负责人: GERALD A HIGGINS
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6098259
• 关键词: Alzheimer's disease; aging; amyloid proteins; brain septal area; cholinergic receptors; gene expression; genetic transcription; growth factor receptors; human tissue; immunocytochemistry; in situ hybridization; mesencephalon; messenger RNA; molecular pathology; neural plasticity; neurotrophic factors; polymerase chain reaction; postmortem; prosencephalon; substantia innominata

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.

该项目解决了 NGF 缺陷是否 反应性可能是某些神经病理学变化的基础 发生在阿尔茨海默病（AD）的基底前脑中。我们建议 检验神经生长因子 (NGF-R) 表达的假设 基因是基础形态完整性的敏感指标 前脑胆碱能神经元（Ch1 - Ch4）细胞群），增加 NGF-R mRNA 水平和神经元肥大与高水平相关 皮质目标区域的 NGF 水平，并降低 NGF-R 和 NGF-R 的水平 神经元萎缩与生长因子剥夺相关。 原位 NGF-R mRNA 的杂交将与定量测量相结合 细胞数量和细胞杂交强度来记录变化 AD 中 Ch1-Ch4 细胞组成分中 NGF-R 基因的表达。 皮质靶点发生淀粉样蛋白沉积的一种机制 区域是通过淀粉样蛋白前体表达的变化 基底层皮质投射胆碱能神经元内的（APP）基因 前脑。 因此，我们将检验以下假设：特定形式的 APP mRNA转录可能优先与NGF-减少相关 阿尔茨海默病的反应性。 这些实验将结合在 使用最近开发的逆转录酶的原位杂交方法 聚合酶链式反应 (R-PCR) 可提供相对定量 AD 中 APP mRNA 比例的变化。