The Olfactory Bulb-Entorhinal Cortex Axis as an Early Biomarker for Alzheimers Disease

嗅球-内嗅皮层轴作为阿尔茨海默病的早期生物标志物

基本信息

批准号：
9250058
负责人：
Ricardo C Araneda
金额：
$ 31.04万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250058
关键词：
Affect Aging Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease model Anatomy Animal Model Appearance Area Back Behavior Behavior assessment Behavioral Biological Markers Brain Cells Characteristics Dementia Detection Development Diagnosis Discrimination Disease Early Diagnosis Electrophysiology (science)Equilibrium Exhibits Feedback Fiber Functional disorder Goals Hippocampus (Brain)Immunohistochemistry Impaired cognition Impairment Label Lateral Learning Light Measurable Memory Memory Loss Molecular Profiling Mus Nerve Degeneration Neurobehavioral Manifestations Neurodegenerative Disorders Neurons Odors Olfactory Cortex Olfactory Pathways Optics Pathologic Pathologic Processes Pathology Pathway interactions Perception Physiological Preventive treatment Process Proteins Research Personnel Rodent Role Series Short-Term Memory Smell Perception Symptoms Synapses Technical Expertise Testing Therapeutic Intervention Transgenic Mice Treatment Efficacy Viral Vulnerable Populations accurate diagnosis biomarker development cell type cellular targeting combat critical period disease diagnosis entorhinal cortex experimental study functional adaptation functional plasticity healthy aging improved interdisciplinary approach mouse model neuropathology neurophysiology normal aging olfactory bulb optogenetics piriform cortex public health relevance relating to nervous system senescence skills tool

项目摘要

DESCRIPTION (provided by applicant): Early detection of Alzheimer's disease (AD) is a critical factor in combating this devastating disease. The discovery that pathological changes underlying brain degeneration and cognitive loss begin at least 10-20 years before dementia onset has provide an important target for the improvement of disease diagnosis and therapy. The development of biomarkers to detect neuropathology associated with early-stage AD will allow the implementation of preventive treatments much earlier in the pathological process, maximizing treatment efficacy. Notably, olfactory dysfunction precedes symptoms of dementia and memory loss, which has made olfactory tests a commonly used tool in early AD detection. As olfactory decline also occurs in normal aging, an accurate diagnosis of AD relies in the proper distinction between these processes. Interestingly, it is well established that the entorhinal-hippocampal circuit, a key pathway for learning and memory, exhibits early neuropathology in AD, and that olfactory information is relayed to the hippocampus via the entorhinal cortex. Unfortunately, the mechanisms underlying olfactory deficits in AD and natural aging remain largely unknown. Here we propose to unravel the mechanisms by which olfactory information is conveyed to the entorhinal cortex and the adaptations that precede olfactory dysfunction in naturally aging mice and in a transgenic mouse model of AD. To achieve this goal, our team of investigators will use a multidisciplinary approach that combines viral-assisted retrograde labeling, electrophysiology, optogenetics, and behavioral assessment.

描述（由适用提供）：早期发现阿尔茨海默氏病（AD）是打击这种破坏性疾病的关键因素。在痴呆症发作之前至少10 - 20年开始的10 - 20年开始，发现病理变化的发现为改善疾病诊断和治疗提供了重要目标。生物标志物检测与早期AD相关的神经病理学的发展将使预防性治疗在病理过程中的实施，从而最大程度地提高治疗效率。值得注意的是，嗅觉功能障碍先于痴呆和记忆力丧失的症状，这使嗅觉测试成为早期AD检测中常用的工具。由于嗅觉下降也发生在正常衰老中，因此AD的准确诊断依赖于这些过程之间的适当区分。有趣的是，众所周知，内嗅 - 海马电路是一种学习和记忆的关键途径，在AD中表现出早期的神经病理学，并且通过内嗅皮层将嗅觉信息传达给海马。不幸的是，AD和自然衰老中嗅觉定义的基本机制在很大程度上尚不清楚。在这里，我们建议揭示嗅觉信息传达给内嗅皮层的机制，以及在自然衰老的小鼠和AD的转基因小鼠模型中嗅觉功能障碍之前的适应性。为了实现这一目标，我们的研究人员将使用多学科的方法，该方法结合了病毒辅助逆行标签，电生理学，光遗传学和行为评估。