AD Concept- OLFACTION AS AN EARLY BIOMARKER OF AD

在嗅觉的四个功能领域（气味识别、辨别、检测和记忆）中，气味识别似乎比AD患者的其他领域受到更强烈的影响。本文提出的研究将探讨蠕虫和小鼠模型系统中AD进展的各个阶段嗅觉功能的参与。拟议的研究将：I）研究烟酰胺腺嘌呤二核苷酸（NAD）补充在ApoE AD秀丽隐杆线虫模型中的作用模式; II）鉴定和表征相对于非AD对照小鼠在AD小鼠的嗅球中差异表达的基因的动力学;和III）分析小鼠中嗅觉功能障碍和AD病理学之间的相关性，作为小鼠年龄和有或没有NAD补充的治疗的函数。这些研究的结果将使用新型蠕虫和已建立的AD小鼠模型来定义AD相关嗅觉缺陷的性质和动力学，并确定嗅觉功能作为NAD补充治疗功效的读出的潜在用途。

Of the four functional domains of olfaction (odor identification, discrimination, detection, and memory), odor identification appears to be more strongly affected than the other domains in AD patients. The studies proposed here will explore the involvement of olfactory functions at various stages of AD progression in worm and mouse model systems. The proposed research will: I) investigate the mode of action of nicotinamide adenine dinucleotide (NAD) supplementation in ApoE AD Caenorhabditis elegans models; II) identify and characterize kinetics of genes differentially expressed in the olfactory bulbs of AD mice relative to non-AD control mice; and III) analyze the correlation between olfactory dysfunction and AD pathology in mice as a function of mouse age and treatment with or without NAD supplementation. The results of these studies will define the nature and kinetics of AD-associated olfactory deficits using novel worm and established mouse models of AD and determine the potential use of olfactory function as a readout for NAD supplementation therapeutic efficacy.