MULTIFOCAL NEURODEGENERATION IN ALZHEIMER'S DISEASE

阿尔茨海默病的多灶性神经变性

• 批准号: 6082539
• 负责人: Brent Alan Vogt
• 金额: $ 25.77万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6082539
• 关键词: Alzheimer's disease; amyloid proteins; behavioral /social science research tag; cingulate gyrus; clinical research; cognition; dementia; human subject; multiinfarct dementia; neocortex; neural degeneration; neurons; neuropsychological tests; neuropsychology; postmortem; protein structure function; remission /regression; short term memory; statistics /biometry; tau proteins

DESCRIPTION: ( Investigator's Abstract): Alzheimer's disease (AD) is thought to terminate in a final common neuropathology with loss of large pyramids, neurofibrillary tangles, and senile plaques. Although well-documented clinical heterogeneity could result from random expression of a single mechanism of cell death, there may be subtypes with unique etiologies. For example, patients with early spastic paraparesis and deletion of exon 9 of the presenilin 1 gene have large, diffuse plaques and degeneration of the corticospinal tract. Also, studies of posterior cingulate cortex fail to confirm the common endpoint hypothesis and multivariate analysis of neurons showed that small-medium pyramids in layers IIIab and IV are often impacted, there is no single laminar pattern of neurodegeneration (LPND), and each LPND has a full range of duration's and little association with neurofibrillary tangles. The proposed studies will use design-based stereology to estimate neuron numbers in the entire cingulate gyrus in controls and early-mild AD cases from Mount Sinai ADRC. This information will be used to test the neuropathological subtypes hypothesis with multivariate models and these will be extended to measures of four domains of cognitive function. The specific aims follow: 1) Estimate neuron numbers in posterior cingulate cortex with systematic and random sampling in 15 control (#1a) and 70 early-mild AD cases (#1b) followed by multivariate analysis. 2) Extend these analyses to anterior cingulate areas and volumetric analysis of areas in temporal, parietal, prefrontal, and occipital cortices. 3) Evaluate the laminar load of amyloid-beta peptides. 4) Evaluate disease progression in LPND with tau immunohistochemistry and disease onset determined with the Clinical Dementia Rating score. 5) Test the subtypes hypothesis by including measures of cognitive and demographic patient characteristics will be tabulated for each neuropathological subtype so that they can be consistently identified and guide studies of the etiology of each.

描述：（研究者摘要）：阿尔茨海默病 (AD)被认为在最终的普通神经病理学中终止， 大金字塔神经系统缠结和老年斑虽然 有充分证据的临床异质性可能是由随机表达的 细胞死亡的单一机制，可能存在具有独特病因的亚型。 例如，患有早期痉挛性下肢轻瘫和外显子9缺失的患者， 早老素1基因具有大的、弥漫性斑块和退化的 皮质脊髓束此外，对后扣带皮层的研究未能 证实了神经元的共同终点假设和多变量分析 表明IIIab和IV层中的中小型金字塔经常受到撞击， 没有单一的层状神经变性模式（LPND），每个LPND 有一个完整的持续时间范围， 缠结。拟议的研究将使用基于设计的体视学来估计 对照组和早期轻度AD患者整个扣带回的神经元数量 来自西奈山ADRC的案例。这些信息将用于测试 神经病理亚型假设与多变量模型，这些将 可以扩展到认知功能的四个领域的测量。具体 目的如下：1）估计后扣带回皮质神经元数目， 对15例对照（#1a）和70例早期轻度AD患者进行系统随机抽样 （#1b）然后进行多变量分析。2)将这些分析扩展到前 扣带区和颞叶，顶叶， 前额叶和枕叶皮层3)评价以下部件的层流载荷 淀粉样β肽4)评估伴有tau蛋白的LPND的疾病进展 免疫组化和疾病发作确定与临床痴呆 评分。5)通过包括以下指标来检验亚型假设： 将对每种患者的认知和人口统计学特征进行制表 神经病理亚型，以便它们可以被一致地识别和指导 每一种的病因学研究。