Structural and Functional Neuroanatomy of Memory in Familial Alzheimer's Disease

家族性阿尔茨海默病记忆的结构和功能神经解剖学

• 批准号: 8128054
• 负责人: Yakeel T. Quiroz
• 金额: $ 2.65万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8128054
• 关键词: Affect; Alzheimer' s Disease; American; Anterior; Area; Behavioral; Biological Markers; Boston; Brain; Brain region; Clinical; Data; Data Set; Dementia; Detection; Deterioration; Diagnostic tests; Disease; Disease Progression; Episodic memory; Exhibits; Face; Functional Magnetic Resonance Imaging; Functional disorder; Gene Mutation; Genes; Goals; Hippocampal Formation; Hippocampus (Brain); Imaging Techniques; Individual; Lead; Learning; Life; Linear Models; Magnetic Resonance Imaging; Measurement; Medial; Memory; Methods; Mutation; Names; Neuroanatomy; Neurobehavioral Manifestations; Neurodegenerative Disorders; Parietal; Parietal Lobe; Pathologic; Pattern; Performance; Pharmaceutical Preparations; Phase; Population; Prefrontal Cortex; Presenile Alzheimer Dementia; Recruitment Activity; Research; Sampling; Staging; Structure; Symptoms; Temporal Lobe; Thick; Training; Universities; Work; base; cerebral atrophy; classical conditioning; early onset; entorhinal cortex; familial Alzheimer disease; insight; morphometry; mutation carrier; neuroimaging; novel; pre-clinical; presenilin-1; tool

DESCRIPTION (provided by applicant): As many as 5.3 million Americans are presently living with Alzheimer's disease (AD). This progressive and fatal neurodegenerative disorder is the most common form of dementia, yet a cure remains elusive. Deterioration of episodic memory is one of the first cognitive symptoms of AD, and has been associated with functional and structural degeneration of the medial temporal lobe regions (MTL). In particular, the hippocampal formation and entorhinal cortex have been shown to be pathologically affected in early phases of AD, even before clinical symptoms are evident. Neuroimaging tools such as structural and functional MRI (sMRI, fMRI) have the potential to identify subtle pathologic changes earlier in the AD progression and could be used as potential biomarkers of AD. The primary goals of this proposal are to use both structural and functional magnetic resonance imaging techniques (sMRI and fMRI) to examine changes in the brains of pre- symptomatic and early-symptomatic individuals who carry a PS1 mutation and who will develop Alzheimer's disease during the 4th decade of life. The PS1 genetic mutation is a fully penetrant, autosomal dominant genetic alteration, meaning that people that carry the PS1 mutation are destined to develop early-onset Alzheimer's disease with near 100% certainty. These subjects therefore provide a unique opportunity to study pre-symptomatic and pre-clinical changes related to Alzheimer's disease. The research proposed in this application will use MRI methods to examine the hypothesis that disease-related changes in the brains of carriers of an Alzheimer's-causing mutation occur within MTL structures in early pre-symptomatic stages of the Alzheimer's disease. This research may lead directly to a diagnostic test that will enable the detection of individuals who will develop sporadic AD later in life, allowing to early initiation of treatments. PUBLIC HEALTH RELEVANCE: I propose to study structural and functional brain changes in pre-symptomatic and early-symptomatic subjects who carry the E280A PS1 mutation and will develop early-onset familial Alzheimer's disease. Structural and functional patterns found in this population have the potential to lead directly to a diagnostic test that can identify those individuals who will later develop sporadic Alzheimer's disease, allowing them to be treated with disease modifying medications before the onset of cognitive symptoms.

描述（由申请人提供）：目前有多达530万美国人患有阿尔茨海默病（AD）。这种进行性和致命的神经退行性疾病是痴呆症最常见的形式，但治疗仍然难以捉摸。情景记忆退化是阿尔茨海默病的首要认知症状之一，并与内侧颞叶区域（MTL）的功能和结构退化有关。特别是，在阿尔茨海默病的早期阶段，甚至在临床症状明显之前，海马体形成和内嗅皮层已被证明受到病理影响。神经成像工具，如结构和功能MRI （sMRI, fMRI）有可能在阿尔茨海默病进展的早期识别细微的病理变化，并可作为阿尔茨海默病的潜在生物标志物。本提案的主要目标是使用结构和功能磁共振成像技术（sMRI和fMRI）来检查携带PS1突变的症状前和症状早期个体的大脑变化，这些个体将在生命的第四个十年中发展为阿尔茨海默病。PS1基因突变是一种完全渗透的常染色体显性基因改变，这意味着携带PS1突变的人几乎100%肯定会患上早发性阿尔茨海默病。因此，这些主题提供了一个独特的机会来研究与阿尔茨海默病相关的症状前和临床前变化。本申请中提出的研究将使用MRI方法来检验一种假设，即在阿尔茨海默病症状前的早期阶段，阿尔茨海默病致病突变携带者的大脑中与疾病相关的变化发生在MTL结构中。这项研究可能会直接导致一种诊断测试，这种测试将能够检测出在生命后期将发展为散发性阿尔茨海默病的个体，从而允许早期开始治疗。